The Microtubule-Associated Rho Activating Factor GEF-H1 Interacts with Exocyst Complex to Regulate Vesicle Traffic

Ritu Pathak, Violaine D. Delorme-Walker, Michael C. Howell, Anthony N. Anselmo, Michael A. White, Gary M. Bokoch, Céline DerMardirossian

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)397-411
Number of pages15
JournalDevelopmental Cell
Volume23
Issue number2
DOIs
StatePublished - Aug 14 2012

Fingerprint

Rho Factor
Microtubules
Rho Guanine Nucleotide Exchange Factors
Chemical activation
Membranes
rho GTP-Binding Proteins
GTP Phosphohydrolases
Exocytosis
Cellular Structures
Cell membranes
Cell Division
Cell Movement
Actins
Cell Membrane
Proteins

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Pathak, R., Delorme-Walker, V. D., Howell, M. C., Anselmo, A. N., White, M. A., Bokoch, G. M., & DerMardirossian, C. (2012). The Microtubule-Associated Rho Activating Factor GEF-H1 Interacts with Exocyst Complex to Regulate Vesicle Traffic. Developmental Cell, 23(2), 397-411. https://doi.org/10.1016/j.devcel.2012.06.014

The Microtubule-Associated Rho Activating Factor GEF-H1 Interacts with Exocyst Complex to Regulate Vesicle Traffic. / Pathak, Ritu; Delorme-Walker, Violaine D.; Howell, Michael C.; Anselmo, Anthony N.; White, Michael A.; Bokoch, Gary M.; DerMardirossian, Céline.

In: Developmental Cell, Vol. 23, No. 2, 14.08.2012, p. 397-411.

Research output: Contribution to journalArticle

Pathak, R, Delorme-Walker, VD, Howell, MC, Anselmo, AN, White, MA, Bokoch, GM & DerMardirossian, C 2012, 'The Microtubule-Associated Rho Activating Factor GEF-H1 Interacts with Exocyst Complex to Regulate Vesicle Traffic', Developmental Cell, vol. 23, no. 2, pp. 397-411. https://doi.org/10.1016/j.devcel.2012.06.014
Pathak, Ritu ; Delorme-Walker, Violaine D. ; Howell, Michael C. ; Anselmo, Anthony N. ; White, Michael A. ; Bokoch, Gary M. ; DerMardirossian, Céline. / The Microtubule-Associated Rho Activating Factor GEF-H1 Interacts with Exocyst Complex to Regulate Vesicle Traffic. In: Developmental Cell. 2012 ; Vol. 23, No. 2. pp. 397-411.
@article{1716a4656d6d4fbdb5a8840297211796,
title = "The Microtubule-Associated Rho Activating Factor GEF-H1 Interacts with Exocyst Complex to Regulate Vesicle Traffic",
abstract = "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.",
author = "Ritu Pathak and Delorme-Walker, {Violaine D.} and Howell, {Michael C.} and Anselmo, {Anthony N.} and White, {Michael A.} and Bokoch, {Gary M.} and C{\'e}line DerMardirossian",
year = "2012",
month = "8",
day = "14",
doi = "10.1016/j.devcel.2012.06.014",
language = "English (US)",
volume = "23",
pages = "397--411",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "2",

}

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

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.

UR - http://www.scopus.com/inward/record.url?scp=84865078112&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865078112&partnerID=8YFLogxK

U2 - 10.1016/j.devcel.2012.06.014

DO - 10.1016/j.devcel.2012.06.014

M3 - Article

VL - 23

SP - 397

EP - 411

JO - Developmental Cell

JF - Developmental Cell

SN - 1534-5807

IS - 2

ER -