Cbln2Cbln4

Cbln2Cbln4 refers to the interaction between cerebellin-2 and cerebellin-4 proteins, members of the cerebellin family of secreted glycoproteins encoded by the CBLN2 and CBLN4 genes. Cerebellins are part of the C1q superfamily and are involved in trans-synaptic signaling that helps organize and maintain synapses in the brain, with a notable emphasis on the cerebellum but also present in other regions.

Biochemically, cerebellins are secreted proteins that can form higher-order oligomers. They are capable of assembling into homo- and heteromeric complexes, including potential Cbln2-Cbln4 assemblies. Through their C1q-like domains, cerebellins can engage with neuronal receptors and adhesion molecules. In the best-characterized system, cerebellins participate in trans-synaptic bridging by interacting with presynaptic neurexins and postsynaptic receptors such as GRID2 (GluD2), a mechanism that supports synapse formation, specificity, and maintenance. The precise receptor partnerships and structural arrangements for Cbln2 and Cbln4, and especially their heteromeric combinations, are an active area of investigation.

Expression of CBLN2 and CBLN4 is documented in the cerebellum and other brain regions, with developmentally regulated patterns that suggest roles in synaptic maturation and plasticity. Functionally, cerebellins contribute to the organization of certain cerebellar circuits, influencing synaptic connectivity and receptor clustering.

Genetic and clinical aspects are areas of ongoing research. Alterations in cerebellin signaling have been explored for possible links to neurodevelopmental and neuropsychiatric conditions, though results are not yet conclusive. Animal models lacking specific cerebellins show synaptic and behavioral phenotypes, underscoring their importance in neural circuit assembly.