9.B.130. The Tetraspan Vesicle Membrane Protein (TVP) Family
Synaptoporins, synaptophysins, synaptogyrins and cellugyrins are homologous major membrane proteins in synaptic vesicles of animals. All have 4 TMSs, belong to the MARVEL domain superfamily in Pfam, and are called tetraspan vesicle membrane proteins (TVPs). They have cytoplasmically located end domains and are ubiquitous and abundant components of vesicles in most, if not all, cells of multicellular organisms (Hübner et al. 2002). They have been shown to form ion conducting ion channels (Woodbury 1995). They are subject to protein modification, e.g., phosphorylation, and are part of multimeric complexes. TVPs contribute to vesicle trafficking and membrane morphogenesis (Hübner et al. 2002).
TVP-containing vesicles shuttle between various membranous compartments and are localized in biosynthetic and endocytotic pathways. Based on gene organization and amino acid sequence similarities, TVPs can be grouped into three distinct families that are referred to as physins, gyrins, and secretory carrier-associated membrane proteins (SCAMPs). In mammals, synaptophysin, synaptoporin, pantophysin, and mitsugumin29 constitute the physins, synaptogyrin 1-4 the gyrins, and SCAMP1-5 the SCAMPs. Members of each family are cell-type-specifically synthesized, resulting in unique patterns of TVP coexpression and subcellular colocalization (Hübner et al. 2002).
TVP orthologs have been identified in most multicellular organisms, including diverse animal and plant species, but have not been detected in unicellular organisms. They are subject to protein modification, most notably to phosphorylation, and are part of multimeric complexes. TVPs contribute to vesicle trafficking and membrane morphogenesis (Hübner et al. 2002). Defects in these proteins may play a role in Schizophrenia.These proteins may function as part of the synaptic vesicle recycling machinery (Abraham et al. 2011).
Synaptobrevin II (sybII) is a key fusogenic molecule on synaptic vesicles (SVs); therefore, the active maintenance of both its conformation and location in sufficient numbers on this organelle is critical in both mediating and sustaining neurotransmitter release. Three proteins play key roles in the presentation, trafficking and retrieval of sybII during the fusion and endocytosis of SVs. The nerve terminal protein α-synuclein catalyses sybII entry into SNARE complexes, whereas the monomeric adaptor protein AP-180 is required for sybII retrieval during SV endocytosis. Overarching these events is the tetraspan SV protein synaptophysin, which is a major sybII interaction partner on the SV. Working models for the control of sybII traffic by synaptophysin and other Sybtraps (sybII trafficking partners) have been proposed, suggesting how dysfunction in sybII traffic may contribute to human diseases (Gordon and Cousin 2014).