Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Cell Sci. 2009 Jul 1;122(Pt 13):2292-9. doi: 10.1242/jcs.046441. Epub 2009 Jun 9.

Functional homology of mammalian syntaxin 16 and yeast Tlg2p reveals a conserved regulatory mechanism.

Author information

  • 1Henry Wellcome Laboratory of Cell Biology, Division of Molecular and Cellular Biology, Davidson Building, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.

Abstract

Membrane fusion in all eukaryotic cells is regulated by the formation of specific SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complexes. The molecular mechanisms that control this process are conserved through evolution and require several protein families, including Sec1p/Munc18 (SM) proteins. Here, we demonstrate that the mammalian SNARE protein syntaxin 16 (Sx16, also known as Syn16) is a functional homologue of the yeast SNARE Tlg2p, in that its expression fully complements the mutant phenotypes of tlg2Delta mutant yeast. We have used this functional homology to demonstrate that, as observed for Tlg2p, the function of Sx16 is regulated by the SM protein Vps45p. Furthermore, in vitro SNARE-complex assembly studies demonstrate that the N-terminal domain of Tlg2p is inhibitory to the formation of SNARE complexes, and that this inhibition can be lifted by the addition of purified Vps45p. By combining these cell-biological and biochemical analyses, we propose an evolutionarily conserved regulatory mechanism for Vps45p function. Our data support a model in which the SM protein is required to facilitate a switch of Tlg2p and Sx16 from a closed to an open conformation, thus allowing SNARE-complex assembly and membrane fusion to proceed.

PMID:
19509055
[PubMed - indexed for MEDLINE]
PMCID:
PMC2723147
Free PMC Article

Images from this publication.See all images (5)Free text

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk