TY - JOUR
T1 - Conflicting views on the membrane fusion machinery and the fusion pore
AU - Sørensen, Jakob B
N1 - Keywords: Animals; Calcium; Exocytosis; Membrane Fusion; Munc18 Proteins; SNARE Proteins; Synaptic Vesicles; Synaptotagmins
PY - 2009
Y1 - 2009
N2 - Fast exocytosis of synaptic vesicles differs from other membrane fusion reactions by being under tight temporal control by the intracellular calcium concentration. This is achieved by subjecting the SNARE-dependent fusion pathway to additional layers of control, both upstream and downstream of the assembly of the fusogenic SNARE-complex. Here, I review conflicting views on the function of the core fusion machinery consisting of the SNAREs, Munc18, complexin, and synaptotagmin. Munc18 controls docking of vesicles to the plasma membrane and initial SNARE-complex assembly, whereas complexin and synaptotagmin cooperate in holding the SNARE complex in an intermediate release-ready or cocked state. Different effects of complexin and synaptotagmin shape the energy landscape for fusion and make final fusion calcium triggered. The final steps are fusion pore formation and expansion, which allow release of the water-soluble vesicle content. The fusion pore remains the most elusive part of the exocytosis pathway, owing to its short lifetime.
AB - Fast exocytosis of synaptic vesicles differs from other membrane fusion reactions by being under tight temporal control by the intracellular calcium concentration. This is achieved by subjecting the SNARE-dependent fusion pathway to additional layers of control, both upstream and downstream of the assembly of the fusogenic SNARE-complex. Here, I review conflicting views on the function of the core fusion machinery consisting of the SNAREs, Munc18, complexin, and synaptotagmin. Munc18 controls docking of vesicles to the plasma membrane and initial SNARE-complex assembly, whereas complexin and synaptotagmin cooperate in holding the SNARE complex in an intermediate release-ready or cocked state. Different effects of complexin and synaptotagmin shape the energy landscape for fusion and make final fusion calcium triggered. The final steps are fusion pore formation and expansion, which allow release of the water-soluble vesicle content. The fusion pore remains the most elusive part of the exocytosis pathway, owing to its short lifetime.
U2 - 10.1146/annurev.cellbio.24.110707.175239
DO - 10.1146/annurev.cellbio.24.110707.175239
M3 - Review
C2 - 19575641
SN - 1081-0706
VL - 25
SP - 513
EP - 537
JO - Annual Review of Cell and Developmental Biology
JF - Annual Review of Cell and Developmental Biology
ER -