Synaptotagmin1, also known as p65, is an integral membrane glycoprotein of neuronal synaptic vesicles and secretory granules of neuroendocrine cells that is widely (but not ubiquitously) expressed in the central and peripheral nervous system. It has a variable N-terminal domain that is exposed to the lumen of the vesicle and a conserved cytoplasmic tail that contains two Ca2+-binding C2-domains.
Ca2+-binding to synaptotagmin triggers exocytosis of synaptic vesicles, thus linking Ca2+-influx during depolarization to neurotransmitter release.
Lumenal antibodies were used in living neurons to label synaptic vesicles from the outside via endocytotic uptake.