Neurexins: Synaptic Cell Surface Proteins Related to the α-Latrotoxin Receptor and Laminin

Abstract

A family of highly polymorphic neuronal cell surface proteins, the neurexins, has been identified. At least two genes for neurexins exist. Each gene uses alternative promoters and multiple variably spliced exons to potentially generate more than a 100 different neurexin transcripts. The neurexins were discovered by the identification of one member of the family as the receptor for alpha-latrotoxin. This toxin is a component of the venom from black widow spiders; it binds to presynaptic nerve terminals and triggers massive neurotransmitter release. Neurexins contain single transmembrane regions and extracellular domains with repeated sequences similar to sequences in laminin A, slit, and agrin, proteins that have been implicated in axon guidance and synaptogenesis. An antibody to neurexin I showed highly concentrated immunoreactivity at the synapse. The polymorphic structure of the neurexins, their neural localization, and their sequence similarity to proteins associated with neurogenesis suggest a function as cell recognition molecules in the nerve terminal.

Age-related expression of Neurexin1 and Neuroligin3 is correlated with presynaptic density in the cerebral cortex and hippocampus of male mice

“…The synaptic proteins neurexins (Nrxns) and neuroligins (Nlgns) have emerged as a pair of fascinating candidates for underlying synaptic plasticity. Presynaptic Nrxns form transsynaptic complexes with postsynaptic Nlgns (Ushkaryov et al 1992;Yamagata et al 2003) and play an important role in differentiation, maturation, and stabilization of both excitatory and inhibitory synapses (Dean et al 2003;Graf et al 2004;Chubykin et al 2007;Budreck and Scheiffele 2007;Krueger et al 2012). These proteins not only facilitate the assembly of functional units on their own side of the synapses but also regulate synaptic specialization on the opposite side of a nascent synapse through their trans-synaptic interactions (Dean and Dresbach 2006).…”

α‐Latrotoxin stimulates glutamate release from cortical astrocytes in cell culture

“…At least one of the receptors is a member of a distinct protein family, the neurexins, which are transmembrane proteins that bind intracellularly to the neuronal synaptic vesicle protein, synaptotagmin [22]. By directly interacting with synaptic proteins a-latrotoxin bypasses the calcium-require-…”

α‐Latrotoxin receptor

“…However, treatment with different glycosidases does not allow to reduce them to electrophoretic bands of the same size [42]. The 29K protein is not related to the 160K and 200K proteins since an antibody against the 29K protein does not recognize any of the larger receptor components [40].…”

“…The information on internal peptide sequences obtained from a mixture of 166220K proteins was used to clone cDNAs representing a novel family of highly polymorphic cell surface membrane proteins which were named neurexins [42]. Neurexin mRNAs were only found in brain-related tissues [42], which perfectly correlates with the distribution of the a-latrotoxin receptor [7].…”

“…4. An antibody, which stains both the 200K and 160K proteins on Western blots, also immunoprecipitates the a-latrotoxin-binding activity from total rat brain extracts [42].…”