TY - JOUR
T1 - The Microtubule-Associated Rho Activating Factor GEF-H1 Interacts with Exocyst Complex to Regulate Vesicle Traffic
AU - Pathak, Ritu
AU - Delorme-Walker, Violaine D.
AU - Howell, Michael C.
AU - Anselmo, Anthony N.
AU - White, Michael A.
AU - Bokoch, Gary M.
AU - DerMardirossian, Céline
N1 - Funding Information:
We dedicate this manuscript to the memory of late Dr. Gary Bokoch, without whose support and guidance this work would not have been possible. We thank Charles Yeaman, Rytis Prekeris, Jennifer Lippincott-Schwartz, Klaus Hahn, and Douglas Lyles for some of the reagents used in this study. We also thank Charles Yeaman for helpful suggestions and advice and Bruce Fowler for assistance with preparation of some DNA constructs. This study was supported by an NIH grant to G.M.B. and C.D.M. (GM39434).
PY - 2012/8/14
Y1 - 2012/8/14
N2 - The exocyst complex plays a critical role in targeting and tethering vesicles to specific sites of the plasma membrane. These events are crucial for polarized delivery of membrane components to the cell surface, which is critical for cell motility and division. Though Rho GTPases are involved in regulating actin dynamics and membrane trafficking, their role in exocyst-mediated vesicle targeting is not very clear. Herein, we present evidence that depletion of GEF-H1, a guanine nucleotide exchange factor for Rho proteins, affects vesicle trafficking. Interestingly, we found that GEF-H1 directly binds to exocyst component Sec5 in a Ral GTPase-dependent manner. This interaction promotes RhoA activation, which then regulates exocyst assembly/localization and exocytosis. Taken together, our work defines a mechanism for RhoA activation in response to RalA-Sec5 signaling and involvement of GEF-H1/RhoA pathway in the regulation of vesicle trafficking.
AB - The exocyst complex plays a critical role in targeting and tethering vesicles to specific sites of the plasma membrane. These events are crucial for polarized delivery of membrane components to the cell surface, which is critical for cell motility and division. Though Rho GTPases are involved in regulating actin dynamics and membrane trafficking, their role in exocyst-mediated vesicle targeting is not very clear. Herein, we present evidence that depletion of GEF-H1, a guanine nucleotide exchange factor for Rho proteins, affects vesicle trafficking. Interestingly, we found that GEF-H1 directly binds to exocyst component Sec5 in a Ral GTPase-dependent manner. This interaction promotes RhoA activation, which then regulates exocyst assembly/localization and exocytosis. Taken together, our work defines a mechanism for RhoA activation in response to RalA-Sec5 signaling and involvement of GEF-H1/RhoA pathway in the regulation of vesicle trafficking.
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U2 - 10.1016/j.devcel.2012.06.014
DO - 10.1016/j.devcel.2012.06.014
M3 - Article
C2 - 22898781
AN - SCOPUS:84865078112
SN - 1534-5807
VL - 23
SP - 397
EP - 411
JO - Developmental cell
JF - Developmental cell
IS - 2
ER -