The Ca2+-triggered fusion of apposed membranes is the defining step in regulated exocytosis. Jens Coorssen and co-workers are studying the involvement of cholesterol, a component of membranes, in this energetically unfavourable step, using a cortical vesicle preparation isolated from sea urchin eggs. Fully primed, release-ready cortical vesicles undergo immediate triggered fusion when the free Ca2+ concentration is increased. The authors show that the removal of cholesterol from the vesicle membranes, its sequestration within membranes, or its enzymatic modification inhibits the extent, Ca2+ sensitivity and kinetics of exocytotic fusion (see ). The addition of exogenous cholesterol or other membrane components that impart negative membrane curvature enables cholesterol-depleted membranes to fuse but does not reinstate the Ca2+ sensitivity or normal kinetics of fusion except at native cholesterol densities. The authors propose, therefore, that cholesterol plays at least two roles in native membrane fusion. They suggest it acts as a membrane organizer that orientates crucial molecular components at the fusion site. In addition, because it affects membrane curvature, cholesterol could directly reduce the energy barriers to fusion.
