RAB3 and synaptotagmin: the yin and yang of synaptic membrane fusion.
Synaptic vesicle exocytosis occurs in consecutive steps: docking, which specifically attaches vesicles to the active zone; priming, which makes the vesicles competent for Ca(2+)-triggered release and may involve a partial fusion reaction; and the final Ca(2+)-regulated step that completes fusion. Recent evidence suggests that the critical regulation of the last step in the reaction is mediated by two proteins with opposite actions: synaptotagmin, a Ca(2+)-binding protein that is essential for Ca(2+)-triggered release and probably serves as the Ca(2+)-sensor in fusion, and rab3, which limits the number of vesicles that can be fused as a function of Ca2+ in order to allow a temporally limited, repeatable signal.
Geppert
M
M
Abteilung Molekulare Neurobiologie, Max-Planck-Institut für experimentelle Medizin, Göttingen, Germany.
Südhof
T C
TC
D000818:Animals; D002135:Calcium-Binding Proteins / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D008561:Membrane Fusion / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000737:chemistry / Q000502:physiology*; D013572:Synaptic Vesicles / Q000737:chemistry / Q000502:physiology; D050857:Synaptotagmins; D020692:rab3 GTP-Binding Proteins
D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D050857:Synaptotagmins; D019204:GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins