Synaptic vesicles participate in a cycle of fusion with the plasma membrane and reformation by endocytosis. Synaptic vesicle protein synaptophysin (SYP) is targeted to early endosomes in transfected fibroblasts and in neuroendocrine cells. SYP is an N-glycosylated intergral membrane protein found in neurons and endocrine cells that associates into hexamers to form a large conductance channel. SYP contains four transmembrane domains and may function as a gap juction-like channel. Membrane cholesterol specfically interacts with SYP to play a role in vesicle formation. Synaptobrevin (VAMP) also binds to SYP and the resultant complex is upregulated during neuronal development, but is absent in exocytosis fusion complex. Thus, the synaptophysin-synaptobrevin complex is not essential for exocytosis, but rather provides a pool of synaptobrevin for exocytosis. In addition, the tail domain of brain Myosin V also forms a stable complex with synaptobrevin II and SYP, and this complex is disassembled upon the depolarization-induced entry of Ca2+ into intact nerve endings.