VAMP4

VAMP4, or vesicle-associated membrane protein 4, is a member of the SNARE family of proteins that mediate membrane fusion events required for intracellular vesicular trafficking. Like other v-SNAREs, VAMP4 is a transmembrane protein that contributes to the fusion of transport vesicles with target membranes, ensuring directionality and specificity in cargo delivery.

Localization and function are centered on endosomal compartments and the trans-Golgi network. VAMP4 is associated with endosomes and participates in retrograde transport from early endosomes to the trans-Golgi network, a pathway important for recycling receptors and sorting hydrolases. It is thought to form SNARE complexes with target-mmembrane t-SNAREs such as syntaxin 6 and Vti1a, enabling the fusion of transport vesicles with the appropriate compartment.

Molecular interactions involve the assembly of a four-helix SNARE bundle that typically includes VAMP4 on the vesicle and syntaxin 6 together with Vti1a on the target membrane, with additional SNARE partners and regulatory proteins modulating complex formation. Through these interactions, VAMP4 contributes to selective trafficking routes within the endolysosomal system and can influence cargo such as receptors and enzymes that pass through the endosomal network.

Expression and regulation of VAMP4 vary by tissue and cell type. Its activity is governed by SNARE complex assembly and orchestration by regulatory factors, and perturbations in VAMP4 function have been associated with defects in endosomal trafficking in experimental systems. Further research continues to clarify its full range of roles in cellular physiology.