The microtubule-associated Rho activating factor GEF-H1 interacts with exocyst complex to regulate vesicle traffic

Dev Cell. 2012 Aug 14;23(2):397-411. doi: 10.1016/j.devcel.2012.06.014.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biological Transport
  • Enzyme Activation
  • Exocytosis*
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism*
  • HeLa Cells
  • Humans
  • Microscopy, Electron, Transmission
  • Microtubules / metabolism*
  • Protein Binding
  • Rho Guanine Nucleotide Exchange Factors
  • Signal Transduction
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • ARHGEF2 protein, human
  • Guanine Nucleotide Exchange Factors
  • Rho Guanine Nucleotide Exchange Factors
  • rhoA GTP-Binding Protein