Protein collar squeezes cell membrane necks

Aurélien Roux of the Curie Institute in Paris and his coworkers in Patricia Basssereau’s group have cleared up one of the mysteries of how the protein dynamin helps form synaptic vesicles. Synaptic vesicles are lipid-wrapped nanoscale packets that contain neurotransmitters, the molecules that convey signals between neurons. Signaling begins when synaptic vesicles fuse with the signaling neuron’s membrane, thereby releasing their contents. The neurotransmitters then diffuse across the tiny gap to the receiving neuron and bind to the neuron’s surface. Once they’ve delivered their message, they unbind and make their way back to the signaling neuron, which retrieves them by budding fresh synaptic vesicles from its cell membrane. The protein clathrin initiates the budding by forming a curved coat on the membrane’s interior surface (see figure); dynamin ties off and ultimately severs the vesicle. In solution, dynamin molecules polymerize into a spiral whose inside radius matches that of the dynamin monomers. In vivo, the spiral is seen to wrap around the necks of clathrin-coated vesicles. Roux and his team set out to determine whether the polymerization is triggered by the neck’s curvature. Their experiment, which used artificial vesicles, optical tweezers, and fluorescently tagged dynamic molecules, showed that dynamin will readily polymerize around tubes whose outside radius matches dynamin’s inside radius. More important, Roux and company also found that when dynamin’s concentration is high enough, it will polymerize on fatter tubes and that the act of polymerizing can apply the few-piconewton force needed to squeeze a neck. (A. Roux et al., Proc. Natl. Acad. Sci. USA 107, 4141, 2010. )—Charles Day