SNCA Protein, Human (His)

alpha-Synuclein (SNCA), a pivotal neuronal protein, orchestrates diverse roles in synaptic activity, including the regulation of synaptic vesicle trafficking and neurotransmitter release. As a monomer, it actively participates in synaptic vesicle exocytosis, enhancing vesicle priming, fusion, and dilation of exocytotic fusion pores, and mechanistically increases local Ca(2+) release from microdomains, crucial for ATP-induced exocytosis. In its multimeric membrane-bound state, SNCA functions as a molecular chaperone, assisting in the folding of synaptic fusion components (SNAREs) at the presynaptic plasma membrane, a process vital for maintaining normal SNARE-complex assembly during aging. SNCA also plays a crucial role in regulating dopamine neurotransmission by interacting with the dopamine transporter (DAT1) and modulating its activity. Existing as both a soluble monomer and homotetramer, a dynamic intracellular population of tetramers and monomers coexists, with the tetramer playing an essential role in maintaining homeostasis. SNCA engages in a complex network of interactions with proteins such as UCHL1, synphilin-1/SNCAIP, CALM1, STXBP1, VAMP2, SNAP25, RPH3A, RAB3A, SERF1A, and SEPTIN4, highlighting its involvement in intricate molecular processes governing synaptic function and integrity.