A molecular network for the transport of the TI-VAMP/VAMP7 vesicles from cell center to periphery

Dev Cell. 2012 Jul 17;23(1):166-80. doi: 10.1016/j.devcel.2012.04.019. Epub 2012 Jun 14.

Abstract

The compartmental organization of eukaryotic cells is maintained dynamically by vesicular trafficking. SNARE proteins play a crucial role in intracellular membrane fusion and need to be targeted to their proper donor or acceptor membrane. The molecular mechanisms that allow for the secretory vesicles carrying the v-SNARE TI-VAMP/VAMP7 to leave the cell center, load onto microtubules, and reach the periphery to mediate exocytosis are largely unknown. Here, we show that the TI-VAMP/VAMP7 partner Varp, a Rab21 guanine nucleotide exchange factor, interacts with GolginA4 and the kinesin 1 Kif5A. Activated Rab21-GTP in turn binds to MACF1, an actin and microtubule regulator, which is itself a partner of GolginA4. These components are required for directed movement of TI-VAMP/VAMP7 vesicles from the cell center to the cell periphery. The molecular mechanisms uncovered here suggest an integrated view of the transport of vesicles carrying a specific v-SNARE toward the cell surface.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Golgi Apparatus / metabolism*
  • Growth Cones / drug effects
  • Growth Cones / metabolism
  • HeLa Cells
  • Humans
  • Kinesins / genetics
  • Kinesins / metabolism
  • Nocodazole / pharmacology
  • Protein Transport / drug effects
  • Protein Transport / physiology*
  • R-SNARE Proteins / metabolism*
  • RNA, Small Interfering / genetics
  • Tubulin Modulators / pharmacology

Substances

  • KIF5A protein, human
  • R-SNARE Proteins
  • RNA, Small Interfering
  • Tubulin Modulators
  • VAMP7 protein, human
  • Kinesins
  • Nocodazole