Neurexins

The neurexin family of cell adhesion proteins consists of three members in vertebrates and has homologs in several invertebrate species. In mammals, each neurexin gene encodes an alpha-neurexin in which the extracellular portion is long, and a beta-neurexin in which the extracellular portion is short. As a result of alternative splicing, both major isoforms can be transcribed in many variants, contributing to distinct structural domains and variability. Neurexins act predominantly at the presynaptic terminal in neurons and play essential roles in neurotransmission and differentiation of synapses. Some of these functions require the formation of trans-synaptic complexes with postsynaptic proteins such as neuroligins, LRRTM proteins or cerebellin. In addition, rare mutations and copy-number variations of human neurexin genes have been linked to autism and schizophrenia, indicating that impairments of synaptic function sustained by neurexins and their binding partners may be relevant to the pathomechanism of these debilitating diseases.