The role of Rab3a in secretory vesicle docking requires association/dissociation of guanidine phosphates and Munc18-1

PLoS One. 2007 Jul 18;2(7):e616. doi: 10.1371/journal.pone.0000616.

Abstract

Rab3a is a small GTPase that binds selectively to secretory vesicles and switches between active, GTP-bound and inactive, GDP-bound conformations. In yeast, Rab and SM-genes interact genetically to promote vesicle targeting/fusion. We tested different Rab3a conformations and genetic interactions with the SM-gene munc18-1 on the docking function of Rab3a in mammalian chromaffin cells. We expressed Rab3a mutants locked in the GTP- or GDP-bound form in wild-type and munc18-1 null mutant cells and analyzed secretory vesicle distribution. We confirmed that wild-type Rab3a promotes vesicle docking in wild-type cells. Unexpectedly, both GTP- and GDP-locked Rab3a mutants did not promote docking. Furthermore, wild-type Rab3a did not promote docking in munc18-1 null cells and GTP- and GDP-Rab3a both decreased the amount of docked vesicles. The results show that GTP- and GDP-locked conformations do not support a Munc18-1 dependent role of Rab3a in docking. This suggests that nucleotide cycling is required to support docking and that this action of Rab3a is upstream of Munc18-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / physiology*
  • Chromaffin Cells / physiology*
  • Cloning, Molecular
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics
  • Guanidine / metabolism*
  • Mice
  • Mice, Knockout
  • Mice, Mutant Strains
  • Munc18 Proteins / metabolism*
  • Secretory Vesicles / physiology*
  • Secretory Vesicles / ultrastructure
  • Semliki forest virus / genetics
  • rab3A GTP-Binding Protein / genetics
  • rab3A GTP-Binding Protein / physiology*

Substances

  • Munc18 Proteins
  • Green Fluorescent Proteins
  • rab3A GTP-Binding Protein
  • Guanidine