Recycling of Synaptic Vesicles.

A widely accepted model describes the synaptic vesicle cycle as a modification of the receptor-mediated recycling pathway present in all cells. This pathway, by which cell surface receptors, like transferrin or low-density lipoprotein receptors, are internalized and recycled back to the surface, involves two distinct vesicular transport steps: clathrin-mediated budding from the plasma membrane and fusion with early endosomes and budding from endosomes of vesicles destined to the plasma membrane. The membrane composition of synaptic vesicles and of clathrin-coated vesicles purified from synaptosomes is very similar. The clathrin adaptor complex AP2, a component of the plasma membrane-derived clathrin coat, binds to synaptotagmin. The paralytic shibire Drosophilu mutants, whose nerve terminals are depleted of synaptic vesicles at the restrictive temperature due to selective impairment of synaptic vesicle endocytosis, harbor mutations in dynamin, a guanosine triphosphatase (GTPase) implicated in clathrin-mediated endocytosis. Fission of clathrin-coated pits to form free vesicles requires dynamin. Dynamin was originally described as a microtubule-binding protein, but its function in synaptic vesicle recycling was revealed when the similarity to the protein encoded by the Drosophilu gene shibire was discovered. Until recently, most studies on synaptic vesicle recycling have focused on the role of proteins. There is increasing evidence, however, for a role of lipids and of phosphoinositides in particular, in synaptic vesicle endocytosis.