title: Membrane fusion protein synexin (annexin VII) as a Ca2+/GTP sensor in exocytotic secretion.
abstract: Exocytotic membrane fusion and secretion are promoted by the concerted action of GTP and Ca2+, although the precise site(s) of action in the process are not presently known. However, the calcium-dependent membrane fusion reaction driven by synexin (annexin VII) is an in vitro model for this process, which we have now found to be further activated by GTP. The mechanism of fusion activation depends on the unique ability of synexin to bind and hydrolyze GTP in a calcium-dependent manner, both in vitro and in vivo in streptolysin O-permeabilized chromaffin cells. The required [Ca2+] for GTP binding by synexin is in the range of 50-200 microM, which is known to occur at exocytotic sites in chromaffin cells, neurons, and other cell types. Previous immunolocalization studies place synexin at exocytotic sites in chromaffin cells, and we conclude that synexin is an atypical G protein that may be responsible for both detecting and mediating the Ca2+/GTP signal for exocytotic membrane fusion.
authors.affiliation: Laboratory of Cell Biology and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: H
authors.initials: H
authors.lastname: Caohuy
authors.forename: M
authors.initials: M
authors.lastname: Srivastava
authors.forename: H B
authors.initials: HB
authors.lastname: Pollard
mesh_terms: D000818:Animals; D017310:Annexin A7 / Q000378:metabolism* / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D002413:Cations, Divalent; D002417:Cattle; D002474:Cell-Free System; D019439:Chromaffin Cells / Q000502:physiology; D002837:Chromaffin Granules / Q000378:metabolism; D005089:Exocytosis; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000502:physiology*; D006801:Humans; D008561:Membrane Fusion; D011994:Recombinant Proteins; D015398:Signal Transduction
chemical_list: D017310:Annexin A7; D002413:Cations, Divalent; D011994:Recombinant Proteins; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; D002118:Calcium