Biomedical Research Education & Training
Faculty Member

MacGurn, Jason, PhD
Assistant Professor of Cell and Developmental Biology

Lab Url: N/A

Phone Number: 615-343-4259

Email Address: jason.a.macgurn@vanderbilt.edu

MacGurn, Jason's picture
Academic history

Office Address   Mailing Address

MRBIII, Rm 4130B


Research Keywords
Membrane Trafficking, Cell Signaling, Ubiquitin Biology, Quantitative Proteomics, Live Cell Imaging,Biochemistry,Cancer,Genetics,Mass spectroscopy,Membrane,Phosphorylation,Post-transcriptional modification,Proteomics,Receptor,Signal transduction,Yeast

Research Specialty
Investigating molecular mechanisms of membrane protein turnover and cell surface remodeling programs in normal and disease states

Research Description
Background

Eukaryotic cells respond to environmental cues by remodeling the cell surface, a process that relies on the targeted removal and degradation of plasma membrane (PM) proteins. This turnover process begins when a transmembrane PM protein (or "cargo") is ubiquitinated, a modification that is recognized by the endocytic machinery and sorted into vesicles. By targeting PM proteins for endocytosis, the cargo ubiquitination machinery directly regulates signaling processes, ion and nutrient homeostasis, stress responses, and protein quality control at the PM. Given that these processes are critical for cell growth and differentiation, it is not surprising that many human disease states, including various cancers, are associated with defects in PM protein turnover.

Research Objective

The main research objective of my lab is to understand the molecular mechanisms that regulate the composition of proteins at the plasma membrane and to engineer new technologies for artificial remodeling of the cell surface.

Cell Surface Remodeling in Yeast

In yeast, ubiquitin-mediated endocytosis is regulated almost exclusively by a ubiquitin ligase called Rsp5, a member of the Nedd4 family ubiquitin ligases. Rsp5 substrate selection is mediated by a modular adaptor network of proteins called ARTs which function to target Rsp5 ubiquitin ligase activity to specific substrates at the cell surface. My lab is focused on understanding (i) the molecular mechanisms that govern regulation of the ART-Rsp5 network and (ii) the biochemical and structural basis of ART-mediated cargo recognition. By dissecting the molecular mechanisms that drive cell surface remodeling in yeast, we hope to better understand cellular strategies for management of biological complexity.

Cell Surface Remodeling in Human Disease

The human genome encodes nine Nedd4 family ubiquitin ligases and many of these have been linked to various human diseases, including cancer. Despite their relevance to human disease, the biological function of many of these ubiquitin ligases is not well understood. Preliminary experiments indicate that networks of adaptor proteins, similar to the ART proteins in yeast, may function to target Nedd4 ubiquitin ligases to specific PM substrates. By characterizing the molecular mechanisms that govern the targeting of Nedd4 ubiquitin ligases in normal and disease states, we aim to develop new technologies that alter cell surface protein composition and explore these as potential tools for therapeutic intervention.

Publications
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, 2, e00459, 2013

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, 31(13), 2882-94, 2012

MacGurn, JA, Hsu, PC, Emr, SD. Ubiquitin and membrane protein turnover: from cradle to grave. Annu Rev Biochem, 81, 231-59, 2012

Manford, AG, Stefan, CJ, Yuan, HL, Macgurn, JA, Emr, SD. ER-to-plasma membrane tethering proteins regulate cell signaling and ER morphology. Dev Cell, 23(6), 1129-40, 2012

MacGurn, JA, Hsu, PC, Smolka, MB, Emr, SD. TORC1 regulates endocytosis via Npr1-mediated phosphoinhibition of a ubiquitin ligase adaptor. Cell, 147(5), 1104-17, 2011

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, 135(4), 714-25, 2008

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, 3(4), e49, 2007

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, 75(6), 2668-78, 2007

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, 3(8), e105, 2007

MacGurn, JA, Raghavan, S, Stanley, SA, Cox, JS. A non-RD1 gene cluster is required for Snm secretion in Mycobacterium tuberculosis. Mol Microbiol, 57(6), 1653-63, 2005


Postdoctoral Position Available
Yes

Postdoctoral Position Details
Interested individuals should inquire via e-mail about postdoctoral research opportunities available in the MacGurn Lab.

Updated Date
08/15/2013