Faculty Appointments
Associate Professor of Cell & Developmental Biology
Education
Ph.D., Biochemistry & Biophysics, University of California, San Francisco, CaliforniaB.A., Biological Sciences, University of Chicago, Chicago, Illinois
Research Description
The MacGurn Lab seeks to understand mechanisms of protein quality control and degradation in eukaryotic cells. A major research objective of my laboratory is to understand how cells regulate ubiquitin metabolism in response to cellular stress and how this regulation contributes to cellular aging. Dissecting these regulatory mechanisms will contribute to our overall understanding of the role of the ubiquitin proteasome system (and its dysregulation) in various human diseases such as neurodegeneration. Having already identified signaling pathways that regulate ubiquitin homeostasis during cellular stress, we are in a strong position to determine how these pathways impact cellular aging and neurodegeneration. In our research we use a variety of quantitative mass spectrometry methodologies to analyze protein abundance, post-translational modifications, and protein interactions in complex networks. We also regularly use in vitro biochemistry to interrogate protein function and live cell imaging methodologies to study cell dynamics.
The MacGurn Lab contains the resources and expertise necessary to conduct model-driven basic research focused on dissecting biochemical and molecular mechanisms of ubiquitination in yeast and human cells. Given our experience characterizing the regulation and substrate targeting mechanisms of ubiquitin ligases we are in a strong position to make significant contributions to the understanding of ubiquitination and deubiquitylation pathways and their role in responding to stress and cellular aging.
The MacGurn Lab contains the resources and expertise necessary to conduct model-driven basic research focused on dissecting biochemical and molecular mechanisms of ubiquitination in yeast and human cells. Given our experience characterizing the regulation and substrate targeting mechanisms of ubiquitin ligases we are in a strong position to make significant contributions to the understanding of ubiquitination and deubiquitylation pathways and their role in responding to stress and cellular aging.
Research Keywords
ubiquitin, membrane trafficking, protein degradation, transporters, aging, lipid metabolism, sphingolipids, mitochondria
Publications
Hepowit NL, Denise AS, MacGurn JA. Use of Deubiquitinase Fusion Proteins to Characterize Endocytic Trafficking in Yeast. Methods Mol Biol. 2023; 2591: 283-95. PMID: 36350555, DOI: 10.1007/978-1-0716-2803-4_17, ISSN: 1940-6029.
Hepowit NL, Kolbe CC, Zelle SR, Latz E, MacGurn JA. Regulation of ubiquitin and ubiquitin-like modifiers by phosphorylation. FEBS J [print-electronic]. 2022 Aug; 289(16): 4797-810. PMID: 34214249, PMCID: PMC9271371, DOI: 10.1111/febs.16101, ISSN: 1742-4658.
Date SS, Xu P, Hepowit NL, Diab NS, Best J, Xie B, Du J, Strieter ER, Jackson LP, MacGurn JA, Graham TR. Ubiquitination drives COPI priming and Golgi SNARE localization. Elife. 2022 Jul 7/29/2022; 11: PMID: 35904239, PMCID: PMC9374436, PII: 80911, DOI: 10.7554/eLife.80911, ISSN: 2050-084X.
Hepowit NL, Macedo JKA, Young LEA, Liu K, Sun RC, MacGurn JA, Dickson RC. Enhancing lifespan of budding yeast by pharmacological lowering of amino acid pools. Aging (Albany NY) [print-electronic]. 2021 Mar 3/21/2021; 13(6): 7846-71. PMID: 33744865, PMCID: PMC8034917, PII: 202849, DOI: 10.18632/aging.202849, ISSN: 1945-4589.
Wong S, Hepowit NL, Port SA, Yau RG, Peng Y, Azad N, Habib A, Harpaz N, Schuldiner M, Hughson FM, MacGurn JA, Weisman LS. Cargo Release from Myosin V Requires the Convergence of Parallel Pathways that Phosphorylate and Ubiquitylate the Cargo Adaptor. Curr Biol [print-electronic]. 2020 Nov 11/16/2020; 30(22): 4399-4412.e7-4412.e7. PMID: 32916113, PMCID: PMC8025699, PII: S0960-9822(20)31252-5, DOI: 10.1016/j.cub.2020.08.062, ISSN: 1879-0445.
Hepowit NL, Pereira KN, Tumolo JM, Chazin WJ, MacGurn JA. Identification of ubiquitin Ser57 kinases regulating the oxidative stress response in yeast. Elife. 2020 Oct 10/19/2020; 9: PMID: 33074099, PMCID: PMC7647399, PII: 58155, DOI: 10.7554/eLife.58155, ISSN: 2050-084X.
Strunk BS, Steinfeld N, Lee S, Jin N, Muñoz-Rivera C, Meeks G, Thomas A, Akemann C, Mapp AK, MacGurn JA, Weisman LS. Roles for a lipid phosphatase in the activation of its opposing lipid kinase. Mol Biol Cell [print-electronic]. 2020 Aug 8/1/2020; 31(17): 1835-45. PMID: 32583743, PMCID: PMC7525815, DOI: 10.1091/mbc.E18-09-0556, ISSN: 1939-4586.
Nielsen CP, MacGurn JA. Coupling Conjugation and Deconjugation Activities to Achieve Cellular Ubiquitin Dynamics. Trends Biochem Sci [print-electronic]. 2020 May; 45(5): 427-39. PMID: 32311336, PMCID: PMC7176742, PII: S0968-0004(20)30030-X, DOI: 10.1016/j.tibs.2020.01.008, ISSN: 0968-0004.
Tumolo JM, Hepowit NL, Joshi SS, MacGurn JA. A Snf1-related nutrient-responsive kinase antagonizes endocytosis in yeast. PLoS Genet. 2020 Mar; 16(3): e1008677. PMID: 32191698, PMCID: PMC7176151, PII: PGENETICS-D-19-01232, DOI: 10.1371/journal.pgen.1008677, ISSN: 1553-7404.
Baile MG, Guiney EL, Sanford EJ, MacGurn JA, Smolka MB, Emr SD. Activity of a ubiquitin ligase adaptor is regulated by disordered insertions in its arrestin domain. Mol Biol Cell [print-electronic]. 2019 Dec 12/1/2019; 30(25): 3057-72. PMID: 31618110, PMCID: PMC6880881, DOI: 10.1091/mbc.E19-08-0451, ISSN: 1939-4586.
Nielsen CP, Jernigan KK, Diggins NL, Webb DJ, MacGurn JA. USP9X Deubiquitylates DVL2 to Regulate WNT Pathway Specification. Cell Rep. 2019 Jul 7/23/2019; 28(4): 1074-1089.e5-1089.e5. PMID: 31340145, PMCID: PMC6884140, PII: S2211-1247(19)30863-0, DOI: 10.1016/j.celrep.2019.06.083, ISSN: 2211-1247.
Lee S, Ho HC, Tumolo JM, Hsu PC, MacGurn JA. Methionine triggers Ppz-mediated dephosphorylation of Art1 to promote cargo-specific endocytosis. J Cell Biol [print-electronic]. 2019 Mar 3/4/2019; 218(3): 977-92. PMID: 30610170, PMCID: PMC6400557, PII: jcb.201712144, DOI: 10.1083/jcb.201712144, ISSN: 1540-8140.
Lee S, Tumolo JM, Ehlinger AC, Jernigan KK, Qualls-Histed SJ, Hsu PC, McDonald WH, Chazin WJ, MacGurn JA. Ubiquitin turnover and endocytic trafficking in yeast are regulated by Ser57 phosphorylation of ubiquitin. Elife. 2017 Nov 11/13/2017; 6: PMID: 29130884, PMCID: PMC5706963, PII: 29176, DOI: 10.7554/eLife.29176, ISSN: 2050-084X.
Xu P, Hankins HM, MacDonald C, Erlinger SJ, Frazier MN, Diab NS, Piper RC, Jackson LP, MacGurn JA, Graham TR. COPI mediates recycling of an exocytic SNARE by recognition of a ubiquitin sorting signal. Elife. 2017 Oct 10/23/2017; 6: PMID: 29058666, PMCID: PMC5663479, PII: 28342, DOI: 10.7554/eLife.28342, ISSN: 2050-084X.
Ho HC, MacGurn JA, Emr SD. Deubiquitinating enzymes Ubp2 and Ubp15 regulate endocytosis by limiting ubiquitination and degradation of ARTs. Mol Biol Cell [print-electronic]. 2017 May 5/1/2017; 28(9): 1271-83. PMID: 28298493, PMCID: PMC5415021, PII: mbc.E17-01-0008, DOI: 10.1091/mbc.E17-01-0008, ISSN: 1939-4586.
MacGurn JA. Garbage on, garbage off: new insights into plasma membrane protein quality control. Curr Opin Cell Biol [print-electronic]. 2014 Aug; 29: 92-8. PMID: 24908345, PMCID: PMC4130900, PII: S0955-0674(14)00054-4, DOI: 10.1016/j.ceb.2014.05.001, ISSN: 1879-0410.
Zhao Y, Macgurn JA, Liu M, Emr S. The ART-Rsp5 ubiquitin ligase network comprises a plasma membrane quality control system that protects yeast cells from proteotoxic stress. Elife. 2013; 2: e00459. PMID: 23599894, PMCID: PMC3628405, PII: 00459, DOI: 10.7554/eLife.00459, ISSN: 2050-084X.
Manford AG, Stefan CJ, Yuan HL, Macgurn JA, Emr SD. ER-to-plasma membrane tethering proteins regulate cell signaling and ER morphology. Dev. Cell. 2012 Dec 12/11/2012; 23(6): 1129-40. PMID: 23237950, PII: S1534-5807(12)00524-2, DOI: 10.1016/j.devcel.2012.11.004, ISSN: 1878-1551.
Ling Y, Stefan CJ, Macgurn JA, Audhya A, Emr SD. The dual PH domain protein Opy1 functions as a sensor and modulator of PtdIns(4,5)P2 synthesis. EMBO J [print-electronic]. 2012 Jun 6/29/2012; 31(13): 2882-94. PMID: 22562153, PMCID: PMC3395088, PII: emboj2012127, DOI: 10.1038/emboj.2012.127, ISSN: 1460-2075.
MacGurn JA, Hsu PC, Emr SD. Ubiquitin and membrane protein turnover: from cradle to grave. Annu. Rev. Biochem [print-electronic]. 2012; 81: 231-59. PMID: 22404628, DOI: 10.1146/annurev-biochem-060210-093619, ISSN: 1545-4509.
MacGurn JA, Hsu PC, Smolka MB, Emr SD. TORC1 regulates endocytosis via Npr1-mediated phosphoinhibition of a ubiquitin ligase adaptor. Cell. 2011 Nov 11/23/2011; 147(5): 1104-17. PMID: 22118465, PII: S0092-8674(11)01271-2, DOI: 10.1016/j.cell.2011.09.054, ISSN: 1097-4172.
Lin CH, MacGurn JA, Chu T, Stefan CJ, Emr SD. Arrestin-related ubiquitin-ligase adaptors regulate endocytosis and protein turnover at the cell surface. Cell [print-electronic]. 2008 Nov 11/14/2008; 135(4): 714-25. PMID: 18976803, PII: S0092-8674(08)01182-3, DOI: 10.1016/j.cell.2008.09.025, ISSN: 1097-4172.
McLaughlin B, Chon JS, MacGurn JA, Carlsson F, Cheng TL, Cox JS, Brown EJ. A mycobacterium ESX-1-secreted virulence factor with unique requirements for export. PLoS Pathog. 2007 Aug 8/3/2007; 3(8): e105. PMID: 17676952, PMCID: PMC1937011, PII: 07-PLPA-RA-0093, DOI: 10.1371/journal.ppat.0030105, ISSN: 1553-7374.
MacGurn JA, Cox JS. A genetic screen for Mycobacterium tuberculosis mutants defective for phagosome maturation arrest identifies components of the ESX-1 secretion system. Infect. Immun [print-electronic]. 2007 Jun; 75(6): 2668-78. PMID: 17353284, PMCID: PMC1932882, PII: IAI.01872-06, DOI: 10.1128/IAI.01872-06, ISSN: 0019-9567.
Greenstein AE, MacGurn JA, Baer CE, Falick AM, Cox JS, Alber T. M. tuberculosis Ser/Thr protein kinase D phosphorylates an anti-anti-sigma factor homolog. PLoS Pathog. 2007 Apr; 3(4): e49. PMID: 17411339, PMCID: PMC1847690, PII: 06-PLPA-RA-0318R3, DOI: 10.1371/journal.ppat.0030049, ISSN: 1553-7374.
MacGurn JA, Raghavan S, Stanley SA, Cox JS. A non-RD1 gene cluster is required for Snm secretion in Mycobacterium tuberculosis. Mol. Microbiol. 2005 Sep; 57(6): 1653-63. PMID: 16135231, PII: MMI4800, DOI: 10.1111/j.1365-2958.2005.04800.x, ISSN: 0950-382X.
Hepowit NL, Kolbe CC, Zelle SR, Latz E, MacGurn JA. Regulation of ubiquitin and ubiquitin-like modifiers by phosphorylation. FEBS J [print-electronic]. 2022 Aug; 289(16): 4797-810. PMID: 34214249, PMCID: PMC9271371, DOI: 10.1111/febs.16101, ISSN: 1742-4658.
Date SS, Xu P, Hepowit NL, Diab NS, Best J, Xie B, Du J, Strieter ER, Jackson LP, MacGurn JA, Graham TR. Ubiquitination drives COPI priming and Golgi SNARE localization. Elife. 2022 Jul 7/29/2022; 11: PMID: 35904239, PMCID: PMC9374436, PII: 80911, DOI: 10.7554/eLife.80911, ISSN: 2050-084X.
Hepowit NL, Macedo JKA, Young LEA, Liu K, Sun RC, MacGurn JA, Dickson RC. Enhancing lifespan of budding yeast by pharmacological lowering of amino acid pools. Aging (Albany NY) [print-electronic]. 2021 Mar 3/21/2021; 13(6): 7846-71. PMID: 33744865, PMCID: PMC8034917, PII: 202849, DOI: 10.18632/aging.202849, ISSN: 1945-4589.
Wong S, Hepowit NL, Port SA, Yau RG, Peng Y, Azad N, Habib A, Harpaz N, Schuldiner M, Hughson FM, MacGurn JA, Weisman LS. Cargo Release from Myosin V Requires the Convergence of Parallel Pathways that Phosphorylate and Ubiquitylate the Cargo Adaptor. Curr Biol [print-electronic]. 2020 Nov 11/16/2020; 30(22): 4399-4412.e7-4412.e7. PMID: 32916113, PMCID: PMC8025699, PII: S0960-9822(20)31252-5, DOI: 10.1016/j.cub.2020.08.062, ISSN: 1879-0445.
Hepowit NL, Pereira KN, Tumolo JM, Chazin WJ, MacGurn JA. Identification of ubiquitin Ser57 kinases regulating the oxidative stress response in yeast. Elife. 2020 Oct 10/19/2020; 9: PMID: 33074099, PMCID: PMC7647399, PII: 58155, DOI: 10.7554/eLife.58155, ISSN: 2050-084X.
Strunk BS, Steinfeld N, Lee S, Jin N, Muñoz-Rivera C, Meeks G, Thomas A, Akemann C, Mapp AK, MacGurn JA, Weisman LS. Roles for a lipid phosphatase in the activation of its opposing lipid kinase. Mol Biol Cell [print-electronic]. 2020 Aug 8/1/2020; 31(17): 1835-45. PMID: 32583743, PMCID: PMC7525815, DOI: 10.1091/mbc.E18-09-0556, ISSN: 1939-4586.
Nielsen CP, MacGurn JA. Coupling Conjugation and Deconjugation Activities to Achieve Cellular Ubiquitin Dynamics. Trends Biochem Sci [print-electronic]. 2020 May; 45(5): 427-39. PMID: 32311336, PMCID: PMC7176742, PII: S0968-0004(20)30030-X, DOI: 10.1016/j.tibs.2020.01.008, ISSN: 0968-0004.
Tumolo JM, Hepowit NL, Joshi SS, MacGurn JA. A Snf1-related nutrient-responsive kinase antagonizes endocytosis in yeast. PLoS Genet. 2020 Mar; 16(3): e1008677. PMID: 32191698, PMCID: PMC7176151, PII: PGENETICS-D-19-01232, DOI: 10.1371/journal.pgen.1008677, ISSN: 1553-7404.
Baile MG, Guiney EL, Sanford EJ, MacGurn JA, Smolka MB, Emr SD. Activity of a ubiquitin ligase adaptor is regulated by disordered insertions in its arrestin domain. Mol Biol Cell [print-electronic]. 2019 Dec 12/1/2019; 30(25): 3057-72. PMID: 31618110, PMCID: PMC6880881, DOI: 10.1091/mbc.E19-08-0451, ISSN: 1939-4586.
Nielsen CP, Jernigan KK, Diggins NL, Webb DJ, MacGurn JA. USP9X Deubiquitylates DVL2 to Regulate WNT Pathway Specification. Cell Rep. 2019 Jul 7/23/2019; 28(4): 1074-1089.e5-1089.e5. PMID: 31340145, PMCID: PMC6884140, PII: S2211-1247(19)30863-0, DOI: 10.1016/j.celrep.2019.06.083, ISSN: 2211-1247.
Lee S, Ho HC, Tumolo JM, Hsu PC, MacGurn JA. Methionine triggers Ppz-mediated dephosphorylation of Art1 to promote cargo-specific endocytosis. J Cell Biol [print-electronic]. 2019 Mar 3/4/2019; 218(3): 977-92. PMID: 30610170, PMCID: PMC6400557, PII: jcb.201712144, DOI: 10.1083/jcb.201712144, ISSN: 1540-8140.
Lee S, Tumolo JM, Ehlinger AC, Jernigan KK, Qualls-Histed SJ, Hsu PC, McDonald WH, Chazin WJ, MacGurn JA. Ubiquitin turnover and endocytic trafficking in yeast are regulated by Ser57 phosphorylation of ubiquitin. Elife. 2017 Nov 11/13/2017; 6: PMID: 29130884, PMCID: PMC5706963, PII: 29176, DOI: 10.7554/eLife.29176, ISSN: 2050-084X.
Xu P, Hankins HM, MacDonald C, Erlinger SJ, Frazier MN, Diab NS, Piper RC, Jackson LP, MacGurn JA, Graham TR. COPI mediates recycling of an exocytic SNARE by recognition of a ubiquitin sorting signal. Elife. 2017 Oct 10/23/2017; 6: PMID: 29058666, PMCID: PMC5663479, PII: 28342, DOI: 10.7554/eLife.28342, ISSN: 2050-084X.
Ho HC, MacGurn JA, Emr SD. Deubiquitinating enzymes Ubp2 and Ubp15 regulate endocytosis by limiting ubiquitination and degradation of ARTs. Mol Biol Cell [print-electronic]. 2017 May 5/1/2017; 28(9): 1271-83. PMID: 28298493, PMCID: PMC5415021, PII: mbc.E17-01-0008, DOI: 10.1091/mbc.E17-01-0008, ISSN: 1939-4586.
MacGurn JA. Garbage on, garbage off: new insights into plasma membrane protein quality control. Curr Opin Cell Biol [print-electronic]. 2014 Aug; 29: 92-8. PMID: 24908345, PMCID: PMC4130900, PII: S0955-0674(14)00054-4, DOI: 10.1016/j.ceb.2014.05.001, ISSN: 1879-0410.
Zhao Y, Macgurn JA, Liu M, Emr S. The ART-Rsp5 ubiquitin ligase network comprises a plasma membrane quality control system that protects yeast cells from proteotoxic stress. Elife. 2013; 2: e00459. PMID: 23599894, PMCID: PMC3628405, PII: 00459, DOI: 10.7554/eLife.00459, ISSN: 2050-084X.
Manford AG, Stefan CJ, Yuan HL, Macgurn JA, Emr SD. ER-to-plasma membrane tethering proteins regulate cell signaling and ER morphology. Dev. Cell. 2012 Dec 12/11/2012; 23(6): 1129-40. PMID: 23237950, PII: S1534-5807(12)00524-2, DOI: 10.1016/j.devcel.2012.11.004, ISSN: 1878-1551.
Ling Y, Stefan CJ, Macgurn JA, Audhya A, Emr SD. The dual PH domain protein Opy1 functions as a sensor and modulator of PtdIns(4,5)P2 synthesis. EMBO J [print-electronic]. 2012 Jun 6/29/2012; 31(13): 2882-94. PMID: 22562153, PMCID: PMC3395088, PII: emboj2012127, DOI: 10.1038/emboj.2012.127, ISSN: 1460-2075.
MacGurn JA, Hsu PC, Emr SD. Ubiquitin and membrane protein turnover: from cradle to grave. Annu. Rev. Biochem [print-electronic]. 2012; 81: 231-59. PMID: 22404628, DOI: 10.1146/annurev-biochem-060210-093619, ISSN: 1545-4509.
MacGurn JA, Hsu PC, Smolka MB, Emr SD. TORC1 regulates endocytosis via Npr1-mediated phosphoinhibition of a ubiquitin ligase adaptor. Cell. 2011 Nov 11/23/2011; 147(5): 1104-17. PMID: 22118465, PII: S0092-8674(11)01271-2, DOI: 10.1016/j.cell.2011.09.054, ISSN: 1097-4172.
Lin CH, MacGurn JA, Chu T, Stefan CJ, Emr SD. Arrestin-related ubiquitin-ligase adaptors regulate endocytosis and protein turnover at the cell surface. Cell [print-electronic]. 2008 Nov 11/14/2008; 135(4): 714-25. PMID: 18976803, PII: S0092-8674(08)01182-3, DOI: 10.1016/j.cell.2008.09.025, ISSN: 1097-4172.
McLaughlin B, Chon JS, MacGurn JA, Carlsson F, Cheng TL, Cox JS, Brown EJ. A mycobacterium ESX-1-secreted virulence factor with unique requirements for export. PLoS Pathog. 2007 Aug 8/3/2007; 3(8): e105. PMID: 17676952, PMCID: PMC1937011, PII: 07-PLPA-RA-0093, DOI: 10.1371/journal.ppat.0030105, ISSN: 1553-7374.
MacGurn JA, Cox JS. A genetic screen for Mycobacterium tuberculosis mutants defective for phagosome maturation arrest identifies components of the ESX-1 secretion system. Infect. Immun [print-electronic]. 2007 Jun; 75(6): 2668-78. PMID: 17353284, PMCID: PMC1932882, PII: IAI.01872-06, DOI: 10.1128/IAI.01872-06, ISSN: 0019-9567.
Greenstein AE, MacGurn JA, Baer CE, Falick AM, Cox JS, Alber T. M. tuberculosis Ser/Thr protein kinase D phosphorylates an anti-anti-sigma factor homolog. PLoS Pathog. 2007 Apr; 3(4): e49. PMID: 17411339, PMCID: PMC1847690, PII: 06-PLPA-RA-0318R3, DOI: 10.1371/journal.ppat.0030049, ISSN: 1553-7374.
MacGurn JA, Raghavan S, Stanley SA, Cox JS. A non-RD1 gene cluster is required for Snm secretion in Mycobacterium tuberculosis. Mol. Microbiol. 2005 Sep; 57(6): 1653-63. PMID: 16135231, PII: MMI4800, DOI: 10.1111/j.1365-2958.2005.04800.x, ISSN: 0950-382X.
Available Postdoctoral Position Details
Posted: 8/15/2013
Interested individuals should inquire via e-mail about postdoctoral research opportunities available in the MacGurn Lab.
Interested individuals should inquire via e-mail about postdoctoral research opportunities available in the MacGurn Lab.