Faculty Appointments
Professor of Molecular Physiology & Biophysics
Education
Ph.D., Cell Biology & Anatomy, University of Tokyo, Tokyo, JapanM.D., Medicine, University of Tokyo, Tokyo, Japan
Office Address
Robinson Research Bldg 766A, Vanderbilt University Medical School
Nashville, TN 37232
Nashville, TN 37232
Research Description
(1) Structure and functional mechanism of macromolecules in the synapses.
The majority of excitatory synaptic transmission in our brain is mediated by the ionotropic glutamate receptors (iGluRs) that are ligand-gated ion channels (also known as AMPA, NMDA and kainite receptors). Functional modulation of glutamate receptors plays pivotal roles in synaptic plasticity, a cellular mechanism contributing to higher cognitive functions such as seen in learning and memory. Dysfunction of glutamate receptors is related to a variety of psychiatric and neurological disorders, including schizophrenia, Alzheimer’s disease, ALS, X-linked mental retardation, intellectual disability and limbic encephalitis. Our goal is to identify the precise mechanism by which these receptors are functionally modified in the brain by combining approaches in molecular and cellular biology, biochemistry, structural biology (cryo-EM). In a recent work we have determined the near atomic structures of AMPA receptor in complex with its auxiliary subunit cornichon (Nakagawa, Science 2019). For a review article see Kamalova and Nakagawa. J. Physiology 2020.
(2) Exploring rules that govern function of circuits.
Studies at the molecular level fall short in elucidating mechanism for cognitive functions, such as learning and memory. We hypothesize that understanding the operation of microcircuits would form bases to develop theoretical rules. Towards this goal, we investigate mechanisms of synaptic plasticity, such as short term dynamics, long term potentiation, and long term depression. We use electrophysiology to record synaptic currents in acute brain slices prepared from genetic model animals in which AMPAR auxiliary subunits are knocked out. In a recent work, we identified and determined the function of a new AMPA receptor auxiliary subunit GSG1L (Shanks, Savas, Maruo, et al. Cell Reports 2012). Our study of GSG1L KO mice tells us that GSG1L modulates AMPA receptor mediated synaptic transmission in the anterior thalamus and its deletion affects cognition as well as seizure susceptibility (Kamalaova et al. Cell Reports, 2020).
(3) Investigation of new AMPA receptor modulators that target auxiliary subunits.
We have completed initial high throughput drug screening and validated hits by electrophysiology (Azumaya et al. PlosOne 2017). We plan to conduct further studies using the brain slices and animals. We also plan to solve the atomic structure of the new compounds in complex with intact AMPA receptors using cryo-EM.
The majority of excitatory synaptic transmission in our brain is mediated by the ionotropic glutamate receptors (iGluRs) that are ligand-gated ion channels (also known as AMPA, NMDA and kainite receptors). Functional modulation of glutamate receptors plays pivotal roles in synaptic plasticity, a cellular mechanism contributing to higher cognitive functions such as seen in learning and memory. Dysfunction of glutamate receptors is related to a variety of psychiatric and neurological disorders, including schizophrenia, Alzheimer’s disease, ALS, X-linked mental retardation, intellectual disability and limbic encephalitis. Our goal is to identify the precise mechanism by which these receptors are functionally modified in the brain by combining approaches in molecular and cellular biology, biochemistry, structural biology (cryo-EM). In a recent work we have determined the near atomic structures of AMPA receptor in complex with its auxiliary subunit cornichon (Nakagawa, Science 2019). For a review article see Kamalova and Nakagawa. J. Physiology 2020.
(2) Exploring rules that govern function of circuits.
Studies at the molecular level fall short in elucidating mechanism for cognitive functions, such as learning and memory. We hypothesize that understanding the operation of microcircuits would form bases to develop theoretical rules. Towards this goal, we investigate mechanisms of synaptic plasticity, such as short term dynamics, long term potentiation, and long term depression. We use electrophysiology to record synaptic currents in acute brain slices prepared from genetic model animals in which AMPAR auxiliary subunits are knocked out. In a recent work, we identified and determined the function of a new AMPA receptor auxiliary subunit GSG1L (Shanks, Savas, Maruo, et al. Cell Reports 2012). Our study of GSG1L KO mice tells us that GSG1L modulates AMPA receptor mediated synaptic transmission in the anterior thalamus and its deletion affects cognition as well as seizure susceptibility (Kamalaova et al. Cell Reports, 2020).
(3) Investigation of new AMPA receptor modulators that target auxiliary subunits.
We have completed initial high throughput drug screening and validated hits by electrophysiology (Azumaya et al. PlosOne 2017). We plan to conduct further studies using the brain slices and animals. We also plan to solve the atomic structure of the new compounds in complex with intact AMPA receptors using cryo-EM.
Research Keywords
Molecular and cellular biophysics of synapses, Structure and function of inotropic glutamate receptors (iGluRs), synaptic plasticity, AMPA receptors, NMDA receptors, ion channel physiology, synaptic physiology, structural biology, electron cryomicroscopy, Cryo-EM, molecular dynamics simulation, drug discovery.
Publications
Ivica J, Kejzar N, Ho H, Stockwell I, Kuchtiak V, Scrutton AM, Nakagawa T, Greger IH. Proton-triggered rearrangement of the AMPA receptor N-terminal domains impacts receptor kinetics and synaptic localization. Nat Struct Mol Biol [print-electronic]. 2024 Aug 8/13/2024; PMID: 39138332, PII: 10.1038/s41594-024-01369-5, DOI: 10.1038/s41594-024-01369-5, ISSN: 1545-9985.
Nakagawa T, Wang XT, Miguez-Cabello FJ, Bowie D. The open gate of the AMPA receptor forms a Ca2+ binding site critical in regulating ion transport. Nat Struct Mol Biol [print-electronic]. 2024 Apr; 31(4): 688-700. PMID: 38409505, PII: 10.1038/s41594-024-01228-3, DOI: 10.1038/s41594-024-01228-3, ISSN: 1545-9985.
Perozzo AM, Schwenk J, Kamalova A, Nakagawa T, Fakler B, Bowie D. GSG1L-containing AMPA receptor complexes are defined by their spatiotemporal expression, native interactome and allosteric sites. Nat Commun. 2023 Oct 10/26/2023; 14(1): 6799. PMID: 37884493, PMCID: PMC10603098, PII: 10.1038/s41467-023-42517-7, DOI: 10.1038/s41467-023-42517-7, ISSN: 2041-1723.
Zhang D, Lape R, Shaikh SA, Kohegyi BK, Watson JF, Cais O, Nakagawa T, Greger IH. Modulatory mechanisms of TARP ¿8-selective AMPA receptor therapeutics. Nat Commun. 2023 Mar 3/25/2023; 14(1): 1659. PMID: 36966141, PMCID: PMC10039940, PII: 10.1038/s41467-023-37259-5, DOI: 10.1038/s41467-023-37259-5, ISSN: 2041-1723.
Singh PK, Cecchini G, Nakagawa T, Iverson TM. CryoEM structure of a post-assembly MS-ring reveals plasticity in stoichiometry and conformation. PLoS One. 2023; 18(5): e0285343. PMID: 37205674, PMCID: PMC10198558, PII: PONE-D-23-07069, DOI: 10.1371/journal.pone.0285343, ISSN: 1932-6203.
Hansen KB, Wollmuth LP, Bowie D, Furukawa H, Menniti FS, Sobolevsky AI, Swanson GT, Swanger SA, Greger IH, Nakagawa T, McBain CJ, Jayaraman V, Low CM, Dell'Acqua ML, Diamond JS, Camp CR, Perszyk RE, Yuan H, Traynelis SF. Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels. Pharmacol Rev. 2021 Oct; 73(4): 298-487. PMID: 34753794, PMCID: PMC8626789, PII: 73/4/298, DOI: 10.1124/pharmrev.120.000131, ISSN: 1521-0081.
Kamalova A, Nakagawa T. AMPA receptor structure and auxiliary subunits. J Physiol [print-electronic]. 2021 Jan; 599(2): 453-69. PMID: 32004381, PMCID: PMC7392800, DOI: 10.1113/JP278701, ISSN: 1469-7793.
Kamalova A, Futai K, Delpire E, Nakagawa T. AMPA Receptor Auxiliary Subunit GSG1L Suppresses Short-Term Facilitation in Corticothalamic Synapses and Determines Seizure Susceptibility. Cell Rep. 2020 Jul 7/21/2020; 32(3): 107921. PMID: 32697982, PMCID: PMC7425083, PII: S2211-1247(20)30902-5, DOI: 10.1016/j.celrep.2020.107921, ISSN: 2211-1247.
Kendall AK, Xie B, Xu P, Wang J, Burcham R, Frazier MN, Binshtein E, Wei H, Graham TR, Nakagawa T, Jackson LP. Mammalian Retromer Is an Adaptable Scaffold for Cargo Sorting from Endosomes. Structure [print-electronic]. 2020 Apr 4/7/2020; 28(4): 393-405.e4-405.e4. PMID: 32027819, PMCID: PMC7145723, PII: S0969-2126(20)30009-5, DOI: 10.1016/j.str.2020.01.009, ISSN: 1878-4186.
Perfitt TL, Wang X, Dickerson MT, Stephenson JR, Nakagawa T, Jacobson DA, Colbran RJ. Neuronal L-Type Calcium Channel Signaling to the Nucleus Requires a Novel CaMKIIa-Shank3 Interaction. J Neurosci [print-electronic]. 2020 Mar 3/4/2020; 40(10): 2000-14. PMID: 32019829, PMCID: PMC7055140, PII: JNEUROSCI.0893-19.2020, DOI: 10.1523/JNEUROSCI.0893-19.2020, ISSN: 1529-2401.
Azumaya CM, Linton EA, Risener CJ, Nakagawa T, Karakas E. Cryo-EM structure of human type-3 inositol triphosphate receptor reveals the presence of a self-binding peptide that acts as an antagonist. J Biol Chem [print-electronic]. 2020 Feb 2/7/2020; 295(6): 1743-53. PMID: 31915246, PMCID: PMC7008357, PII: S0021-9258(17)49871-1, DOI: 10.1074/jbc.RA119.011570, ISSN: 1083-351X.
Nakagawa T. Structures of the AMPA receptor in complex with its auxiliary subunit cornichon. Science. 2019 Dec 12/6/2019; 366(6470): 1259-63. PMID: 31806817, PII: 366/6470/1259, DOI: 10.1126/science.aay2783, ISSN: 1095-9203.
Sierra-Valdez F, Azumaya CM, Romero LO, Nakagawa T, Cordero-Morales JF. Structure-function analyses of the ion channel TRPC3 reveal that its cytoplasmic domain allosterically modulates channel gating. J Biol Chem [print-electronic]. 2018 Oct 10/12/2018; 293(41): 16102-14. PMID: 30139744, PMCID: PMC6187627, PII: S0021-9258(20)35148-6, DOI: 10.1074/jbc.RA118.005066, ISSN: 1083-351X.
Azumaya CM, Sierra-Valdez F, Cordero-Morales JF, Nakagawa T. Cryo-EM structure of the cytoplasmic domain of murine transient receptor potential cation channel subfamily C member 6 (TRPC6). J Biol Chem [print-electronic]. 2018 Jun 6/29/2018; 293(26): 10381-91. PMID: 29752403, PMCID: PMC6028952, PII: S0021-9258(20)33871-0, DOI: 10.1074/jbc.RA118.003183, ISSN: 1083-351X.
Wang X, Marks CR, Perfitt TL, Nakagawa T, Lee A, Jacobson DA, Colbran RJ. A novel mechanism for Ca2+/calmodulin-dependent protein kinase II targeting to L-type Ca2+ channels that initiates long-range signaling to the nucleus. J Biol Chem [print-electronic]. 2017 Oct 10/20/2017; 292(42): 17324-36. PMID: 28916724, PMCID: PMC5655510, PII: S0021-9258(20)33891-6, DOI: 10.1074/jbc.M117.788331, ISSN: 1083-351X.
Hawken NM, Zaika EI, Nakagawa T. Engineering defined membrane-embedded elements of AMPA receptor induces opposing gating modulation by cornichon 3 and stargazin. J Physiol [print-electronic]. 2017 Oct 10/15/2017; 595(20): 6517-39. PMID: 28815591, PMCID: PMC5638889, DOI: 10.1113/JP274897, ISSN: 1469-7793.
Stephenson JR, Wang X, Perfitt TL, Parrish WP, Shonesy BC, Marks CR, Mortlock DP, Nakagawa T, Sutcliffe JS, Colbran RJ. A Novel Human CAMK2A Mutation Disrupts Dendritic Morphology and Synaptic Transmission, and Causes ASD-Related Behaviors. J Neurosci [print-electronic]. 2017 Feb 2/22/2017; 37(8): 2216-33. PMID: 28130356, PMCID: PMC5338762, PII: JNEUROSCI.2068-16.2017, DOI: 10.1523/JNEUROSCI.2068-16.2017, ISSN: 1529-2401.
Azumaya CM, Days EL, Vinson PN, Stauffer S, Sulikowski G, Weaver CD, Nakagawa T. Screening for AMPA receptor auxiliary subunit specific modulators. PLoS One. 2017; 12(3): e0174742. PMID: 28358902, PMCID: PMC5373622, PII: PONE-D-16-47312, DOI: 10.1371/journal.pone.0174742, ISSN: 1932-6203.
Elegheert J, Kakegawa W, Clay JE, Shanks NF, Behiels E, Matsuda K, Kohda K, Miura E, Rossmann M, Mitakidis N, Motohashi J, Chang VT, Siebold C, Greger IH, Nakagawa T, Yuzaki M, Aricescu AR. Structural basis for integration of GluD receptors within synaptic organizer complexes. Science. 2016 Jul 7/15/2016; 353(6296): 295-9. PMID: 27418511, PMCID: PMC5291321, PII: 353/6296/295, DOI: 10.1126/science.aae0104, ISSN: 1095-9203.
Coles CH, Mitakidis N, Zhang P, Elegheert J, Lu W, Stoker AW, Nakagawa T, Craig AM, Jones EY, Aricescu AR. Structural basis for extracellular cis and trans RPTPs signal competition in synaptogenesis. Nat Commun. 2014 Nov 11/11/2014; 5: 5209. PMID: 25385546, PMCID: PMC4239663, PII: ncomms6209, DOI: 10.1038/ncomms6209, ISSN: 2041-1723.
Shanks NF, Cais O, Maruo T, Savas JN, Zaika EI, Azumaya CM, Yates JR, Greger I, Nakagawa T. Molecular dissection of the interaction between the AMPA receptor and cornichon homolog-3. J Neurosci. 2014 Sep 9/3/2014; 34(36): 12104-20. PMID: 25186755, PMCID: PMC4152608, PII: 34/36/12104, DOI: 10.1523/JNEUROSCI.0595-14.2014, ISSN: 1529-2401.
Shanks NF, Savas JN, Maruo T, Cais O, Hirao A, Oe S, Ghosh A, Noda Y, Greger IH, Yates JR, Nakagawa T. Differences in AMPA and kainate receptor interactomes facilitate identification of AMPA receptor auxiliary subunit GSG1L. Cell Rep [print-electronic]. 2012 Jun 6/28/2012; 1(6): 590-8. PMID: 22813734, PMCID: PMC3401968, PII: S2211-1247(12)00128-3, DOI: 10.1016/j.celrep.2012.05.004, ISSN: 2211-1247.
Farina AN, Blain KY, Maruo T, Kwiatkowski W, Choe S, Nakagawa T. Separation of domain contacts is required for heterotetrameric assembly of functional NMDA receptors. J. Neurosci. 2011 Mar 3/9/2011; 31(10): 3565-79. PMID: 21389213, PMCID: PMC3063151, PII: 31/10/3565, DOI: 10.1523/JNEUROSCI.6041-10.2011, ISSN: 1529-2401.
Nakagawa T, Hoogenraad CC. Lentiviral transgenesis. Methods Mol. Biol. 2011; 693: 117-42. PMID: 21080278, DOI: 10.1007/978-1-60761-974-1_8, ISSN: 1940-6029.
Nakagawa T. The biochemistry, ultrastructure, and subunit assembly mechanism of AMPA receptors. Mol. Neurobiol [print-electronic]. 2010 Dec; 42(3): 161-84. PMID: 21080238, PMCID: PMC2992128, DOI: 10.1007/s12035-010-8149-x, ISSN: 1559-1182.
Comoletti D, Miller MT, Jeffries CM, Wilson J, Demeler B, Taylor P, Trewhella J, Nakagawa T. The macromolecular architecture of extracellular domain of alphaNRXN1: domain organization, flexibility, and insights into trans-synaptic disposition. Structure. 2010 Aug 8/11/2010; 18(8): 1044-53. PMID: 20696403, PMCID: PMC2948785, PII: S0969-2126(10)00234-0, DOI: 10.1016/j.str.2010.06.005, ISSN: 1878-4186.
Shanks NF, Maruo T, Farina AN, Ellisman MH, Nakagawa T. Contribution of the global subunit structure and stargazin on the maturation of AMPA receptors. J. Neurosci. 2010 Feb 2/17/2010; 30(7): 2728-40. PMID: 20164357, PMCID: PMC2842908, PII: 30/7/2728, DOI: 10.1523/JNEUROSCI.5146-09.2010, ISSN: 1529-2401.
Fischer A, Garcia-Rodriguez C, Geren I, Lou J, Marks JD, Nakagawa T, Montal M. Molecular architecture of botulinum neurotoxin E revealed by single particle electron microscopy. J. Biol. Chem [print-electronic]. 2008 Feb 2/15/2008; 283(7): 3997-4003. PMID: 18032388, PII: M707917200, DOI: 10.1074/jbc.M707917200, ISSN: 0021-9258.
Cheng D, Hoogenraad CC, Rush J, Ramm E, Schlager MA, Duong DM, Xu P, Wijayawardana SR, Hanfelt J, Nakagawa T, Sheng M, Peng J. Relative and absolute quantification of postsynaptic density proteome isolated from rat forebrain and cerebellum. Mol. Cell Proteomics [print-electronic]. 2006 Jun; 5(6): 1158-70. PMID: 16507876, PII: D500009-MCP200, DOI: 10.1074/mcp.D500009-MCP200, ISSN: 1535-9476.
Nakagawa T, Feliu-Mojer MI, Wulf P, Lois C, Sheng M, Hoogenraad CC. Generation of lentiviral transgenic rats expressing glutamate receptor interacting protein 1 (GRIP1) in brain, spinal cord and testis. J. Neurosci. Methods [print-electronic]. 2006 Apr 4/15/2006; 152(1-2): 1-9. PMID: 16157387, PII: S0165-0270(05)00279-7, DOI: 10.1016/j.jneumeth.2005.08.001, ISSN: 0165-0270.
Nakagawa T, Cheng Y, Sheng M, Walz T. Three-dimensional structure of an AMPA receptor without associated stargazin/TARP proteins. Biol. Chem. 2006 Feb; 387(2): 179-87. PMID: 16497150, DOI: 10.1515/BC.2006.024, ISSN: 1431-6730.
Chen X, Vinade L, Leapman RD, Petersen JD, Nakagawa T, Phillips TM, Sheng M, Reese TS. Mass of the postsynaptic density and enumeration of three key molecules. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2005 Aug 8/9/2005; 102(32): 11551-6. PMID: 16061821, PMCID: PMC1182136, PII: 0505359102, DOI: 10.1073/pnas.0505359102, ISSN: 0027-8424.
Takao K, Okamoto K, Nakagawa T, Neve RL, Nagai T, Miyawaki A, Hashikawa T, Kobayashi S, Hayashi Y. Visualization of synaptic Ca2+ /calmodulin-dependent protein kinase II activity in living neurons. J. Neurosci. 2005 Mar 3/23/2005; 25(12): 3107-12. PMID: 15788767, PII: 25/12/3107, DOI: 10.1523/JNEUROSCI.0085-05.2005, ISSN: 1529-2401.
Nakagawa T, Cheng Y, Ramm E, Sheng M, Walz T. Structure and different conformational states of native AMPA receptor complexes. Nature. 2005 Feb 2/3/2005; 433(7025): 545-9. PMID: 15690046, PII: nature03328, DOI: 10.1038/nature03328, ISSN: 1476-4687.
Nakagawa T, Futai K, Lashuel HA, Lo I, Okamoto K, Walz T, Hayashi Y, Sheng M. Quaternary structure, protein dynamics, and synaptic function of SAP97 controlled by L27 domain interactions. Neuron. 2004 Oct 10/28/2004; 44(3): 453-67. PMID: 15504326, PII: S089662730400649X, DOI: 10.1016/j.neuron.2004.10.012, ISSN: 0896-6273.
Nakagawa T, Engler JA, Sheng M. The dynamic turnover and functional roles of alpha-actinin in dendritic spines. Neuropharmacology. 2004 Oct; 47(5): 734-45. PMID: 15458845, PII: S002839080400214X, DOI: 10.1016/j.neuropharm.2004.07.022, ISSN: 0028-3908.
Schulz TW, Nakagawa T, Licznerski P, Pawlak V, Kolleker A, Rozov A, Kim J, Dittgen T, Köhr G, Sheng M, Seeburg PH, Osten P. Actin/alpha-actinin-dependent transport of AMPA receptors in dendritic spines: role of the PDZ-LIM protein RIL. J. Neurosci. 2004 Sep 9/29/2004; 24(39): 8584-94. PMID: 15456832, PII: 24/39/8584, DOI: 10.1523/JNEUROSCI.2100-04.2004, ISSN: 1529-2401.
Passafaro M, Nakagawa T, Sala C, Sheng M. Induction of dendritic spines by an extracellular domain of AMPA receptor subunit GluR2. Nature. 2003 Aug 8/7/2003; 424(6949): 677-81. PMID: 12904794, PII: nature01781, DOI: 10.1038/nature01781, ISSN: 1476-4687.
Sheng M, Nakagawa T. Neurobiology: glutamate receptors on the move. Nature. 2002 Jun 6/6/2002; 417(6889) Sect. 601,2.
Nakajima K, Takei Y, Tanaka Y, Nakagawa T, Nakata T, Noda Y, Setou M, Hirokawa N. Molecular motor KIF1C is not essential for mouse survival and motor-dependent retrograde Golgi apparatus-to-endoplasmic reticulum transport. Mol. Cell. Biol. 2002 Feb; 22(3): 866-73. PMID: 11784862, PMCID: PMC133549, ISSN: 0270-7306.
Zhao C, Takita J, Tanaka Y, Setou M, Nakagawa T, Takeda S, Yang HW, Terada S, Nakata T, Takei Y, Saito M, Tsuji S, Hayashi Y, Hirokawa N. Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta. Cell. 2001 Jun 6/1/2001; 105(5): 587-97. PMID: 11389829, PII: S0092-8674(01)00363-4, ISSN: 0092-8674.
Nakagawa T, Sheng M. Neurobiology. A stargazer foretells the way to the synapse. Science. 2000 Dec 12/22/2000; 290(5500): 2270-1. PMID: 11188726, ISSN: 0036-8075.
Nakagawa T, Setou M, Seog D, Ogasawara K, Dohmae N, Takio K, Hirokawa N. A novel motor, KIF13A, transports mannose-6-phosphate receptor to plasma membrane through direct interaction with AP-1 complex. Cell. 2000 Nov 11/10/2000; 103(4): 569-81. PMID: 11106728, PII: S0092-8674(00)00161-6, ISSN: 0092-8674.
Setou M, Nakagawa T, Seog DH, Hirokawa N. Kinesin superfamily motor protein KIF17 and mLin-10 in NMDA receptor-containing vesicle transport. Science. 2000 Jun 6/9/2000; 288(5472): 1796-802. PMID: 10846156, PII: 8578, ISSN: 0036-8075.
Nakagawa T, Tanaka Y, Matsuoka E, Kondo S, Okada Y, Noda Y, Kanai Y, Hirokawa N. Identification and classification of 16 new kinesin superfamily (KIF) proteins in mouse genome. Proc. Natl. Acad. Sci. U.S.A. 1997 Sep 9/2/1997; 94(18): 9654-9. PMID: 9275178, PMCID: PMC23244, ISSN: 0027-8424.
Nakagawa T, Chen J, Zhang Z, Kanai Y, Hirokawa N. Two distinct functions of the carboxyl-terminal tail domain of NF-M upon neurofilament assembly: cross-bridge formation and longitudinal elongation of filaments. J. Cell Biol. 1995 Apr; 129(2): 411-29. PMID: 7721944, PMCID: PMC2199923, ISSN: 0021-9525.
Nakagawa T, Wang XT, Miguez-Cabello FJ, Bowie D. The open gate of the AMPA receptor forms a Ca2+ binding site critical in regulating ion transport. Nat Struct Mol Biol [print-electronic]. 2024 Apr; 31(4): 688-700. PMID: 38409505, PII: 10.1038/s41594-024-01228-3, DOI: 10.1038/s41594-024-01228-3, ISSN: 1545-9985.
Perozzo AM, Schwenk J, Kamalova A, Nakagawa T, Fakler B, Bowie D. GSG1L-containing AMPA receptor complexes are defined by their spatiotemporal expression, native interactome and allosteric sites. Nat Commun. 2023 Oct 10/26/2023; 14(1): 6799. PMID: 37884493, PMCID: PMC10603098, PII: 10.1038/s41467-023-42517-7, DOI: 10.1038/s41467-023-42517-7, ISSN: 2041-1723.
Zhang D, Lape R, Shaikh SA, Kohegyi BK, Watson JF, Cais O, Nakagawa T, Greger IH. Modulatory mechanisms of TARP ¿8-selective AMPA receptor therapeutics. Nat Commun. 2023 Mar 3/25/2023; 14(1): 1659. PMID: 36966141, PMCID: PMC10039940, PII: 10.1038/s41467-023-37259-5, DOI: 10.1038/s41467-023-37259-5, ISSN: 2041-1723.
Singh PK, Cecchini G, Nakagawa T, Iverson TM. CryoEM structure of a post-assembly MS-ring reveals plasticity in stoichiometry and conformation. PLoS One. 2023; 18(5): e0285343. PMID: 37205674, PMCID: PMC10198558, PII: PONE-D-23-07069, DOI: 10.1371/journal.pone.0285343, ISSN: 1932-6203.
Hansen KB, Wollmuth LP, Bowie D, Furukawa H, Menniti FS, Sobolevsky AI, Swanson GT, Swanger SA, Greger IH, Nakagawa T, McBain CJ, Jayaraman V, Low CM, Dell'Acqua ML, Diamond JS, Camp CR, Perszyk RE, Yuan H, Traynelis SF. Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels. Pharmacol Rev. 2021 Oct; 73(4): 298-487. PMID: 34753794, PMCID: PMC8626789, PII: 73/4/298, DOI: 10.1124/pharmrev.120.000131, ISSN: 1521-0081.
Kamalova A, Nakagawa T. AMPA receptor structure and auxiliary subunits. J Physiol [print-electronic]. 2021 Jan; 599(2): 453-69. PMID: 32004381, PMCID: PMC7392800, DOI: 10.1113/JP278701, ISSN: 1469-7793.
Kamalova A, Futai K, Delpire E, Nakagawa T. AMPA Receptor Auxiliary Subunit GSG1L Suppresses Short-Term Facilitation in Corticothalamic Synapses and Determines Seizure Susceptibility. Cell Rep. 2020 Jul 7/21/2020; 32(3): 107921. PMID: 32697982, PMCID: PMC7425083, PII: S2211-1247(20)30902-5, DOI: 10.1016/j.celrep.2020.107921, ISSN: 2211-1247.
Kendall AK, Xie B, Xu P, Wang J, Burcham R, Frazier MN, Binshtein E, Wei H, Graham TR, Nakagawa T, Jackson LP. Mammalian Retromer Is an Adaptable Scaffold for Cargo Sorting from Endosomes. Structure [print-electronic]. 2020 Apr 4/7/2020; 28(4): 393-405.e4-405.e4. PMID: 32027819, PMCID: PMC7145723, PII: S0969-2126(20)30009-5, DOI: 10.1016/j.str.2020.01.009, ISSN: 1878-4186.
Perfitt TL, Wang X, Dickerson MT, Stephenson JR, Nakagawa T, Jacobson DA, Colbran RJ. Neuronal L-Type Calcium Channel Signaling to the Nucleus Requires a Novel CaMKIIa-Shank3 Interaction. J Neurosci [print-electronic]. 2020 Mar 3/4/2020; 40(10): 2000-14. PMID: 32019829, PMCID: PMC7055140, PII: JNEUROSCI.0893-19.2020, DOI: 10.1523/JNEUROSCI.0893-19.2020, ISSN: 1529-2401.
Azumaya CM, Linton EA, Risener CJ, Nakagawa T, Karakas E. Cryo-EM structure of human type-3 inositol triphosphate receptor reveals the presence of a self-binding peptide that acts as an antagonist. J Biol Chem [print-electronic]. 2020 Feb 2/7/2020; 295(6): 1743-53. PMID: 31915246, PMCID: PMC7008357, PII: S0021-9258(17)49871-1, DOI: 10.1074/jbc.RA119.011570, ISSN: 1083-351X.
Nakagawa T. Structures of the AMPA receptor in complex with its auxiliary subunit cornichon. Science. 2019 Dec 12/6/2019; 366(6470): 1259-63. PMID: 31806817, PII: 366/6470/1259, DOI: 10.1126/science.aay2783, ISSN: 1095-9203.
Sierra-Valdez F, Azumaya CM, Romero LO, Nakagawa T, Cordero-Morales JF. Structure-function analyses of the ion channel TRPC3 reveal that its cytoplasmic domain allosterically modulates channel gating. J Biol Chem [print-electronic]. 2018 Oct 10/12/2018; 293(41): 16102-14. PMID: 30139744, PMCID: PMC6187627, PII: S0021-9258(20)35148-6, DOI: 10.1074/jbc.RA118.005066, ISSN: 1083-351X.
Azumaya CM, Sierra-Valdez F, Cordero-Morales JF, Nakagawa T. Cryo-EM structure of the cytoplasmic domain of murine transient receptor potential cation channel subfamily C member 6 (TRPC6). J Biol Chem [print-electronic]. 2018 Jun 6/29/2018; 293(26): 10381-91. PMID: 29752403, PMCID: PMC6028952, PII: S0021-9258(20)33871-0, DOI: 10.1074/jbc.RA118.003183, ISSN: 1083-351X.
Wang X, Marks CR, Perfitt TL, Nakagawa T, Lee A, Jacobson DA, Colbran RJ. A novel mechanism for Ca2+/calmodulin-dependent protein kinase II targeting to L-type Ca2+ channels that initiates long-range signaling to the nucleus. J Biol Chem [print-electronic]. 2017 Oct 10/20/2017; 292(42): 17324-36. PMID: 28916724, PMCID: PMC5655510, PII: S0021-9258(20)33891-6, DOI: 10.1074/jbc.M117.788331, ISSN: 1083-351X.
Hawken NM, Zaika EI, Nakagawa T. Engineering defined membrane-embedded elements of AMPA receptor induces opposing gating modulation by cornichon 3 and stargazin. J Physiol [print-electronic]. 2017 Oct 10/15/2017; 595(20): 6517-39. PMID: 28815591, PMCID: PMC5638889, DOI: 10.1113/JP274897, ISSN: 1469-7793.
Stephenson JR, Wang X, Perfitt TL, Parrish WP, Shonesy BC, Marks CR, Mortlock DP, Nakagawa T, Sutcliffe JS, Colbran RJ. A Novel Human CAMK2A Mutation Disrupts Dendritic Morphology and Synaptic Transmission, and Causes ASD-Related Behaviors. J Neurosci [print-electronic]. 2017 Feb 2/22/2017; 37(8): 2216-33. PMID: 28130356, PMCID: PMC5338762, PII: JNEUROSCI.2068-16.2017, DOI: 10.1523/JNEUROSCI.2068-16.2017, ISSN: 1529-2401.
Azumaya CM, Days EL, Vinson PN, Stauffer S, Sulikowski G, Weaver CD, Nakagawa T. Screening for AMPA receptor auxiliary subunit specific modulators. PLoS One. 2017; 12(3): e0174742. PMID: 28358902, PMCID: PMC5373622, PII: PONE-D-16-47312, DOI: 10.1371/journal.pone.0174742, ISSN: 1932-6203.
Elegheert J, Kakegawa W, Clay JE, Shanks NF, Behiels E, Matsuda K, Kohda K, Miura E, Rossmann M, Mitakidis N, Motohashi J, Chang VT, Siebold C, Greger IH, Nakagawa T, Yuzaki M, Aricescu AR. Structural basis for integration of GluD receptors within synaptic organizer complexes. Science. 2016 Jul 7/15/2016; 353(6296): 295-9. PMID: 27418511, PMCID: PMC5291321, PII: 353/6296/295, DOI: 10.1126/science.aae0104, ISSN: 1095-9203.
Coles CH, Mitakidis N, Zhang P, Elegheert J, Lu W, Stoker AW, Nakagawa T, Craig AM, Jones EY, Aricescu AR. Structural basis for extracellular cis and trans RPTPs signal competition in synaptogenesis. Nat Commun. 2014 Nov 11/11/2014; 5: 5209. PMID: 25385546, PMCID: PMC4239663, PII: ncomms6209, DOI: 10.1038/ncomms6209, ISSN: 2041-1723.
Shanks NF, Cais O, Maruo T, Savas JN, Zaika EI, Azumaya CM, Yates JR, Greger I, Nakagawa T. Molecular dissection of the interaction between the AMPA receptor and cornichon homolog-3. J Neurosci. 2014 Sep 9/3/2014; 34(36): 12104-20. PMID: 25186755, PMCID: PMC4152608, PII: 34/36/12104, DOI: 10.1523/JNEUROSCI.0595-14.2014, ISSN: 1529-2401.
Shanks NF, Savas JN, Maruo T, Cais O, Hirao A, Oe S, Ghosh A, Noda Y, Greger IH, Yates JR, Nakagawa T. Differences in AMPA and kainate receptor interactomes facilitate identification of AMPA receptor auxiliary subunit GSG1L. Cell Rep [print-electronic]. 2012 Jun 6/28/2012; 1(6): 590-8. PMID: 22813734, PMCID: PMC3401968, PII: S2211-1247(12)00128-3, DOI: 10.1016/j.celrep.2012.05.004, ISSN: 2211-1247.
Farina AN, Blain KY, Maruo T, Kwiatkowski W, Choe S, Nakagawa T. Separation of domain contacts is required for heterotetrameric assembly of functional NMDA receptors. J. Neurosci. 2011 Mar 3/9/2011; 31(10): 3565-79. PMID: 21389213, PMCID: PMC3063151, PII: 31/10/3565, DOI: 10.1523/JNEUROSCI.6041-10.2011, ISSN: 1529-2401.
Nakagawa T, Hoogenraad CC. Lentiviral transgenesis. Methods Mol. Biol. 2011; 693: 117-42. PMID: 21080278, DOI: 10.1007/978-1-60761-974-1_8, ISSN: 1940-6029.
Nakagawa T. The biochemistry, ultrastructure, and subunit assembly mechanism of AMPA receptors. Mol. Neurobiol [print-electronic]. 2010 Dec; 42(3): 161-84. PMID: 21080238, PMCID: PMC2992128, DOI: 10.1007/s12035-010-8149-x, ISSN: 1559-1182.
Comoletti D, Miller MT, Jeffries CM, Wilson J, Demeler B, Taylor P, Trewhella J, Nakagawa T. The macromolecular architecture of extracellular domain of alphaNRXN1: domain organization, flexibility, and insights into trans-synaptic disposition. Structure. 2010 Aug 8/11/2010; 18(8): 1044-53. PMID: 20696403, PMCID: PMC2948785, PII: S0969-2126(10)00234-0, DOI: 10.1016/j.str.2010.06.005, ISSN: 1878-4186.
Shanks NF, Maruo T, Farina AN, Ellisman MH, Nakagawa T. Contribution of the global subunit structure and stargazin on the maturation of AMPA receptors. J. Neurosci. 2010 Feb 2/17/2010; 30(7): 2728-40. PMID: 20164357, PMCID: PMC2842908, PII: 30/7/2728, DOI: 10.1523/JNEUROSCI.5146-09.2010, ISSN: 1529-2401.
Fischer A, Garcia-Rodriguez C, Geren I, Lou J, Marks JD, Nakagawa T, Montal M. Molecular architecture of botulinum neurotoxin E revealed by single particle electron microscopy. J. Biol. Chem [print-electronic]. 2008 Feb 2/15/2008; 283(7): 3997-4003. PMID: 18032388, PII: M707917200, DOI: 10.1074/jbc.M707917200, ISSN: 0021-9258.
Cheng D, Hoogenraad CC, Rush J, Ramm E, Schlager MA, Duong DM, Xu P, Wijayawardana SR, Hanfelt J, Nakagawa T, Sheng M, Peng J. Relative and absolute quantification of postsynaptic density proteome isolated from rat forebrain and cerebellum. Mol. Cell Proteomics [print-electronic]. 2006 Jun; 5(6): 1158-70. PMID: 16507876, PII: D500009-MCP200, DOI: 10.1074/mcp.D500009-MCP200, ISSN: 1535-9476.
Nakagawa T, Feliu-Mojer MI, Wulf P, Lois C, Sheng M, Hoogenraad CC. Generation of lentiviral transgenic rats expressing glutamate receptor interacting protein 1 (GRIP1) in brain, spinal cord and testis. J. Neurosci. Methods [print-electronic]. 2006 Apr 4/15/2006; 152(1-2): 1-9. PMID: 16157387, PII: S0165-0270(05)00279-7, DOI: 10.1016/j.jneumeth.2005.08.001, ISSN: 0165-0270.
Nakagawa T, Cheng Y, Sheng M, Walz T. Three-dimensional structure of an AMPA receptor without associated stargazin/TARP proteins. Biol. Chem. 2006 Feb; 387(2): 179-87. PMID: 16497150, DOI: 10.1515/BC.2006.024, ISSN: 1431-6730.
Chen X, Vinade L, Leapman RD, Petersen JD, Nakagawa T, Phillips TM, Sheng M, Reese TS. Mass of the postsynaptic density and enumeration of three key molecules. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2005 Aug 8/9/2005; 102(32): 11551-6. PMID: 16061821, PMCID: PMC1182136, PII: 0505359102, DOI: 10.1073/pnas.0505359102, ISSN: 0027-8424.
Takao K, Okamoto K, Nakagawa T, Neve RL, Nagai T, Miyawaki A, Hashikawa T, Kobayashi S, Hayashi Y. Visualization of synaptic Ca2+ /calmodulin-dependent protein kinase II activity in living neurons. J. Neurosci. 2005 Mar 3/23/2005; 25(12): 3107-12. PMID: 15788767, PII: 25/12/3107, DOI: 10.1523/JNEUROSCI.0085-05.2005, ISSN: 1529-2401.
Nakagawa T, Cheng Y, Ramm E, Sheng M, Walz T. Structure and different conformational states of native AMPA receptor complexes. Nature. 2005 Feb 2/3/2005; 433(7025): 545-9. PMID: 15690046, PII: nature03328, DOI: 10.1038/nature03328, ISSN: 1476-4687.
Nakagawa T, Futai K, Lashuel HA, Lo I, Okamoto K, Walz T, Hayashi Y, Sheng M. Quaternary structure, protein dynamics, and synaptic function of SAP97 controlled by L27 domain interactions. Neuron. 2004 Oct 10/28/2004; 44(3): 453-67. PMID: 15504326, PII: S089662730400649X, DOI: 10.1016/j.neuron.2004.10.012, ISSN: 0896-6273.
Nakagawa T, Engler JA, Sheng M. The dynamic turnover and functional roles of alpha-actinin in dendritic spines. Neuropharmacology. 2004 Oct; 47(5): 734-45. PMID: 15458845, PII: S002839080400214X, DOI: 10.1016/j.neuropharm.2004.07.022, ISSN: 0028-3908.
Schulz TW, Nakagawa T, Licznerski P, Pawlak V, Kolleker A, Rozov A, Kim J, Dittgen T, Köhr G, Sheng M, Seeburg PH, Osten P. Actin/alpha-actinin-dependent transport of AMPA receptors in dendritic spines: role of the PDZ-LIM protein RIL. J. Neurosci. 2004 Sep 9/29/2004; 24(39): 8584-94. PMID: 15456832, PII: 24/39/8584, DOI: 10.1523/JNEUROSCI.2100-04.2004, ISSN: 1529-2401.
Passafaro M, Nakagawa T, Sala C, Sheng M. Induction of dendritic spines by an extracellular domain of AMPA receptor subunit GluR2. Nature. 2003 Aug 8/7/2003; 424(6949): 677-81. PMID: 12904794, PII: nature01781, DOI: 10.1038/nature01781, ISSN: 1476-4687.
Sheng M, Nakagawa T. Neurobiology: glutamate receptors on the move. Nature. 2002 Jun 6/6/2002; 417(6889) Sect. 601,2.
Nakajima K, Takei Y, Tanaka Y, Nakagawa T, Nakata T, Noda Y, Setou M, Hirokawa N. Molecular motor KIF1C is not essential for mouse survival and motor-dependent retrograde Golgi apparatus-to-endoplasmic reticulum transport. Mol. Cell. Biol. 2002 Feb; 22(3): 866-73. PMID: 11784862, PMCID: PMC133549, ISSN: 0270-7306.
Zhao C, Takita J, Tanaka Y, Setou M, Nakagawa T, Takeda S, Yang HW, Terada S, Nakata T, Takei Y, Saito M, Tsuji S, Hayashi Y, Hirokawa N. Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta. Cell. 2001 Jun 6/1/2001; 105(5): 587-97. PMID: 11389829, PII: S0092-8674(01)00363-4, ISSN: 0092-8674.
Nakagawa T, Sheng M. Neurobiology. A stargazer foretells the way to the synapse. Science. 2000 Dec 12/22/2000; 290(5500): 2270-1. PMID: 11188726, ISSN: 0036-8075.
Nakagawa T, Setou M, Seog D, Ogasawara K, Dohmae N, Takio K, Hirokawa N. A novel motor, KIF13A, transports mannose-6-phosphate receptor to plasma membrane through direct interaction with AP-1 complex. Cell. 2000 Nov 11/10/2000; 103(4): 569-81. PMID: 11106728, PII: S0092-8674(00)00161-6, ISSN: 0092-8674.
Setou M, Nakagawa T, Seog DH, Hirokawa N. Kinesin superfamily motor protein KIF17 and mLin-10 in NMDA receptor-containing vesicle transport. Science. 2000 Jun 6/9/2000; 288(5472): 1796-802. PMID: 10846156, PII: 8578, ISSN: 0036-8075.
Nakagawa T, Tanaka Y, Matsuoka E, Kondo S, Okada Y, Noda Y, Kanai Y, Hirokawa N. Identification and classification of 16 new kinesin superfamily (KIF) proteins in mouse genome. Proc. Natl. Acad. Sci. U.S.A. 1997 Sep 9/2/1997; 94(18): 9654-9. PMID: 9275178, PMCID: PMC23244, ISSN: 0027-8424.
Nakagawa T, Chen J, Zhang Z, Kanai Y, Hirokawa N. Two distinct functions of the carboxyl-terminal tail domain of NF-M upon neurofilament assembly: cross-bridge formation and longitudinal elongation of filaments. J. Cell Biol. 1995 Apr; 129(2): 411-29. PMID: 7721944, PMCID: PMC2199923, ISSN: 0021-9525.
Available Postdoctoral Position Details
Posted: 10/18/2012
Postdoctoral positions are available. Detail information can be found at the following URL: http://www.mc.vanderbilt.edu/root/vumc.php?site=terunaganakagawa
Postdoctoral positions are available. Detail information can be found at the following URL: http://www.mc.vanderbilt.edu/root/vumc.php?site=terunaganakagawa