Calsyntenin-3 (CLSTN3)

Calsyntenin-3 (CLSTN3) is an atypical cadherin family member and type I membrane protein primarily expressed in neurons[1][2][3]. It functions as a postsynaptic cell adhesion molecule that interacts directly with presynaptic neurexins (α- and β-neurexins), mediating and regulating the development of both excitatory and inhibitory synaptic connections in distinct neural circuits[1][2][3]. Uniquely, CLSTN3 regulates the balance between excitatory and inhibitory synapse numbers in individual neurons: it inhibits the formation of excitatory parallel-fiber synapses while promoting inhibitory synapse formation, thereby helping maintain neural circuit stability and function[1][3]. In addition to its key role at the postsynaptic membrane, some evidence suggests an alternative function as a presynaptic adaptor for kinesin-dependent axonal transport, although this remains under debate[1]. Structurally, CLSTN3 contains two extracellular cadherin domains, a single LNS (laminin, neurexin, sex hormone-binding globulin-like) domain, a transmembrane region, and a short cytoplasmic tail[1]. Mutations or dysregulation of CLSTN3 have been associated with autism spectrum disorders, underlining its significance in neural development and disease[3]. A variant, CLSTN3β, is expressed in adipocytes and may play a role in thermogenesis, but the canonical neuronal isoform is best characterized for its synaptic roles[3]. No known drugs are established to directly target Calsyntenin-3, and it is not currently considered a direct therapeutic target, but research continues into its involvement in neurological and psychiatric disorders and synaptic function[1][2][3].

Other names

Calsyntenin-3CLSTN3CS3KIAA0726Alc-betaCSTN3CDHR14Alcadein-betacadherin-related family member 14alcbetaalc-betaalcadein beta