Synaptophysin ‐dependent synaptobrevin‐2 trafficking at the presynapse‐Mechanism and function

Synaptophysin (Syp) is the second most abundant protein on synaptic vesicles at the presynapse, however its physiological role has remained elusive. This review summarises proposed roles of Syp, and proposes that its sole function is to control the endocytic retrieval of synaptobrevin-2 (Syb2). It also provides a unifying model, outlining how Syp directs Syb2 trafficking in collaboration with other key players such as intersectin-1 and adaptor protein 180 (AP180)/clathrin assembly lymphoid myeloid leukaemia (CALM). The review concludes with a series of perspectives and unaddressed questions relating to Syp-dependent Syb2 trafficking in health and disease. Abbreviations: AP-2, adaptor protein complex 2; NSF, NEM-sensitive factor; SNAP-25, synaptosomal-associated protein 25kDa; α-SNAP, α-soluble NSF-attachment protein; Syx1, syntaxin 1. AbstractSynaptobrevin-2 (Syb2) is a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) that is essential for neurotransmitter release. It is the most numerous protein on a synaptic vesicle (SV) and drives SV fusion via interactions with its cognate SNARE partners on the presynaptic plasma membrane. Synaptophysin (Syp) is the second most abundant protein on SVs; however, in contrast to Syb2, it has no obligatory role in neurotransmission. Syp interacts with Syb2 on SVs, and the molecular nature of its interaction with Syb2 and its physiological role has been debated for decades. However, recent studies have revealed t...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: REVIEW ARTICLE Source Type: research