Neurexin

neurexin 1
3D ribbon diagram of alpha-neurexin 1
Identifiers
Symbol	NRXN1
Entrez	9378
HUGO	8008
OMIM	600565
RefSeq	NM_001135659.1
UniProt	Q9ULB1
Other data
Locus	Chr. 2 p16.3

Neurexin (NRXN) is a presynaptic protein that helps to connect neurons at the synapse. They are located mostly on the presynaptic membrane and contain a single transmembrane domain. The extracellular domain interacts with proteins in the synaptic cleft, most notably neuroligin, while the intracellular cytoplasmic portion interacts with proteins associated with exocytosis. Neurexin and neuroligin "shake hands," resulting in the connection between the two neurons and the production of a synapse. Neurexins mediate signaling across the synapse, and influence the properties of neural networks by synapse specificity. Neurexins were discovered as receptors for α-latrotoxin, a vertebrate-specific toxin in black widow spider venom that binds to presynaptic receptors and induces massive neurotransmitter release. In humans, alterations in genes encoding neurexins are implicated in autism and other cognitive diseases, such as Tourette syndrome and schizophrenia.

In mammals, neurexin is encoded by three different genes (NRXN1, 2, and 3) each controlled by two different promoters (an upstream α and a downstream β promoter) resulting in α-neurexins 1-3 and β-neurexins 1-3. In addition, there are alternative splicing at 5 sites in α-neurexin and 2 in β-neurexin, more than 2000 splice variants are possible, suggesting its role in determining synapse specificity.

The encoded proteins are structurally similar to laminin, slit, and agrin, other proteins involved in axon guidance and synaptogenesis. α-Neurexins and β-neurexins have identical intracellular domains but different extracellular domains. The extracellular domain of α-neurexin is composed of three neurexin repeats which each contain LNS (laminin, nectin, sex-hormone binding globulin) – EGF (epidermal growth factor) – LNS domains. N1α binds to a variety of ligands including neuroligins and GABA receptors, though neurons of every receptor type express neurexins. β-Neurexins are shorter versions of α-neurexins, containing only one LNS domain. β-Neurexins (located presynaptically) act as receptors for neuroligin (located postsynaptically). Additionally, β-Neurexin has also been found to play a role in angiogenesis.