Calsyntenin-1, a proteolytically processed postsynaptic membrane protein with a cytoplasmic calcium-binding domain

In a screen for proteins released from synapse-forming spinal cord neurons, we found the proteolytically cleaved N-terminal fragment of a transmembran e protein localized in the postsynaptic membrane of both excitatory and inh ibitory synapses. We termed this protein calsyntenin-1, because it binds sy naptic Ca2+ with its cytoplasmic domain. By binding Ca2+, calsyntenin-1 may modulate Ca2+-mediated postsynaptic signals. Proteolytic cleavage of calsy ntenin-1 in its extracellular moiety generates a transmembrane stump that i s internalized and accumulated in the spine apparatus of spine synapses. Th erefore, the synaptic Ca2+ modulation by calsyntenin-1 may be subject to re gulation by extracellular proteolysis in the synaptic cleft. Thus, calsynte nin-1 may link extracellular proteolysis in the synaptic cleft and postsyna ptic Ca2+ signaling.