Specific interactions of Mss4 with members of the Rab GTPase subfamily

Janet L. Burton, Marie E Burns, Evelina Gatti, George J. Augustine, Pietro De Camilli

Research output: Contribution to journalArticle

102 Scopus citations

Abstract

Mss4 is a mammalian protein that was identified as a suppressor of a yeast secretory mutant harboring a mutation in the GTPase Sec4 and was found to stimulate GDP release from this protein. We have now performed a biochemical characterization of the Mss4 protein and examined the specificity of its association with mammalian GTPases. Mss4 is primarily a soluble protein with a widespread tissue distribution. Recombinant Mss4 binds GTPases present in tissue extracts, and by a gel overlay assay binds specifically Rab Rab10proteins. We further define the Mss4-GTPase interaction to a subset of Rabs belonging to the same subfamily branch which include Rab1, Rab3, Rab8, Rab10, Sec4 and Ypt1 but not Rab2, Rab4, Rab5, Rab6, Rab9 and Rab11. Accordingly, Mss4 co-precipitates from a brain extract with Rab3a but not Rab5. Mss4 only stimulates GDP release from, and the association of GTPγS with, this Rab subset. Recombinant Mss4 and Rab3a form a stable complex in solution that is dissociated with either GDP or GTPγS. Injection of Mss4 into the squid giant nerve terminal enhances neurotransmitter release. These results suggest that Mss4 behaves as a guanylnucleotide exchange factor (GEF) for a subset of Rabs to influence distinct vesicular transport steps along the secretory pathway.

Original languageEnglish (US)
Pages (from-to)5547-5558
Number of pages12
JournalEMBO Journal
Volume13
Issue number23
StatePublished - Dec 1 1994
Externally publishedYes

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Keywords

  • GEF
  • GFR
  • ras
  • Squid
  • Synaptic vesicles

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

Burton, J. L., Burns, M. E., Gatti, E., Augustine, G. J., & De Camilli, P. (1994). Specific interactions of Mss4 with members of the Rab GTPase subfamily. EMBO Journal, 13(23), 5547-5558.