The fusion pores of Ca2+ -triggered exocytosis

Abstract

The aqueous compartment inside a vesicle makes its first connection with the extracellular fluid through an intermediate structure termed the exocytotic fusion pore. Progress in exocytosis can be measured in terms of the formation and growth of the fusion pore. The fusion pore has become a major focus of research in exocytosis; sensitive biophysical measurements have provided various glimpses of what it looks like and how it behaves. Some of the principal questions about the molecular mechanism of exocytosis can be cast explicitly in terms of properties and transitions of fusion pores. This Review will present current knowledge about fusion pores in Ca(2+)-triggered exocytosis, highlight recent advances and relate questions about fusion pores to broader issues concerning how cells regulate exocytosis and how nerve terminals release neurotransmitter.

Figure 1

Two models of membrane fusion. (a, i) Proteins capable of forming a fusion pore are present in the vesicle and plasma membranes. (ii) These proteins associate into a closed pore. (iii) A conformational change in this complex opens the pore. (iv) The lipid bilayers merge through a remodeling of the two lipid bilayers. (b) Lipid fusion according to the stalk model. (i) Lipid bilayers are pulled together. In regulated exocytosis, proteins (not shown) exert the necessary force. (ii) An initial merger stage forms, in which the outer leaflets remodel to form a stalk. (iii) The outer leaflets draw apart and the inner leaflets form a bilayer in this hemifusion diaphragm. (iv) A pore forms in the new bilayer of inner leaflets.

Figure 2

A model of the fusion pore formed by the membrane anchors of syntaxin. A barrel of five to eight membrane anchors can form a fusion pore with a conductance consistent with experimental measurements; six are shown here (top). The SNARE motifs radiate outward from the pore. The fusion pore through the vesicle membrane and the t-SNARE components are not shown. The residues where mutations alter fusion pore flux and conductance fall along one face of a helical wheel formed from the membrane anchor. Residues implicated as lining the pore are highlighted in yellow (bottom).