Complexin

Complexin is a family of small, highly conserved cytosolic proteins that regulate neurotransmitter release at chemical synapses. In mammals, there are four genes encoding complexins: CPLX1, CPLX2, CPLX3, and CPLX4, commonly referred to as complexins I–IV. These proteins are expressed in the nervous system with varying regional patterns, and they function as essential modulators of SNARE-mediated exocytosis.

Complexins interact with the SNARE complex formed by syntaxin-1, SNAP-25, and VAMP2 (synaptobrevin). They bind through a central helical domain and have additional N- and C-terminal regions that influence their regulatory effects. A widely described role is to act as a clamp that reduces spontaneous (Ca2+-independent) vesicle fusion, thereby decreasing background neurotransmitter release. At the same time, complexins promote rapid, Ca2+-triggered neurotransmitter release by stabilizing a primed SNARE complex and working in concert with synaptotagmin-1 to facilitate fusion when Ca2+ enters the presynaptic terminal. The precise contribution of each isoform and the balance between clamping and facilitation can vary among synapses and brain regions.

Structure and expression: Complexins are roughly 110–140 amino acids in length. The conserved central SNARE-binding domain is flanked by variable regions that modulate localization and regulatory activity. CPLX1 and CPLX2 are broadly expressed in the central nervous system, whereas CPLX3 and CPLX4 show more restricted patterns, including retina and cerebellum.

Genetic and physiological studies in model systems show that loss or alteration of complexin disrupts evoked release and can increase spontaneous fusion, underscoring its central role in the timing and efficiency of synaptic transmission. Dysregulation of complexin expression or function has been investigated in the context of neurological disorders, reflecting its importance in fast synaptic signaling.

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