Neurexin-neuroligin signaling in synapse development.
Neurexins and neuroligins are emerging as central organizing molecules for excitatory glutamatergic and inhibitory GABAergic synapses in mammalian brain. They function as cell adhesion molecules, bridging the synaptic cleft. Remarkably, each partner can trigger formation of a hemisynapse: neuroligins trigger presynaptic differentiation and neurexins trigger postsynaptic differentiation. Recent protein interaction assays and cell culture studies indicate a selectivity of function conferred by alternative splicing in both partners. An insert at site 4 of beta-neurexins selectively promotes GABAergic synaptic function, whereas an insert at site B of neuroligin 1 selectively promotes glutamatergic synaptic function. Initial knockdown and knockout studies indicate that neurexins and neuroligins have an essential role in synaptic transmission, particularly at GABAergic synapses, but further studies are needed to assess the in vivo functions of these complex protein families.
Craig
Ann Marie
AM
Brain Research Centre, University of British Columbia, 2211 Wesbrook Mall, Vancouver V6T 2B5, Canada. amcraig@interchange.ubc.ca
Kang
Yunhee
Y
D000818:Animals; D001921:Brain / Q000196:embryology* / Q000378:metabolism* / Q000648:ultrastructure; D015816:Cell Adhesion Molecules, Neuronal; D002454:Cell Differentiation / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D015816:Cell Adhesion Molecules, Neuronal; D006023:Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D020033:Protein Isoforms; C112162:neurexophilin; C093438:neuroligin 1; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid