Vesicle-associated membrane protein 4 (VAMP4) is a v-SNARE protein involved in intracellular membrane trafficking and synaptic vesicle recycling. In non-neuronal cells, it is predominantly localized to the trans-Golgi network (TGN), but is also present on endosomes, transport vesicles, and secretory compartments. VAMP4 participates in trafficking between endosomes and the TGN [1, 2].
In neurons, VAMP4 is present on synaptic vesicles, has a specialized role in presynaptic membrane trafficking and neurotransmitter release and is required for efficient formation of synaptic vesicles [3]. VAMP4-containing vesicles have also been associated with asynchronous neurotransmitter release, distinguishing their function from that of VAMP2, which predominantly supports rapid synchronous release [4].
The trafficking of VAMP4 is regulated by sorting signals, including a di-leucine motif, which contributes to its endocytic retrieval and intracellular targeting [2,4]. Following intense neuronal activity, VAMP4 can be sorted toward endolysosomal compartments or recycled into synaptic vesicles, with this sorting influencing presynaptic release probability [5].
VAMP4 was shown to be enriched in TGN-associated tubular and vesicular membranes and to form SNARE complexes with syntaxin 6 [1].
