MEMBRANE-FUSION PROTEIN SYNEXIN (ANNEXIN-VII) AS A CA2+ GTP SENSOR INEXOCYTOTIC SECRETION/

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 membr ane fusion reaction driven by synexin (annexin VII) is an in vitro mod el for this process, which we have now found to be further activated b y GTP, The mechanism of fusion activation depends on the unique abilit y of synexin to bind and hydrolyze GTP in a calcium-dependent manner, both in vitro and in vivo in streptolysin O-permeabilized chromaffin c ells, The required [Ca2+] for GTP binding by synexin is in the range o f 50-200 mu M, which is known to occur at exocytotic sites in chromaff in cells, neurons, and other cell types, Previous immunolocalization s tudies place synexin at exocytotic sites in chromaffin cells, and we c onclude that synexin is an atypical G protein that may be responsible for both detecting and mediating the Ca2+/GTP signal for exocytotic me mbrane fusion.