Alternative splicing controls selective trans-synaptic interactions of the neuroligin-neurexin complex.
Formation of synapses requires specific cellular interactions that organize pre- and postsynaptic compartments. The neuroligin-neurexin complex mediates heterophilic adhesion and can trigger assembly of glutamatergic and GABAergic synapses in cultured hippocampal neurons. Both neuroligins and neurexins are encoded by multiple genes. Alternative splicing generates large numbers of isoforms, which may engage in selective axo-dendritic interactions. We explored whether alternative splicing of the postsynaptic neuroligins modifies their activity toward glutamatergic and GABAergic axons. We find that small extracellular splice insertions restrict the function of neuroligin-1 and -2 to glutamatergic and GABAergic contacts and alter interaction with presynaptic neurexins. The neuroligin isoforms associated with GABAergic contacts bind to neurexin-1alpha and a subset of neurexin-1betas. In turn, these neurexin isoforms induce GABAergic but not glutamatergic postsynaptic differentiation. Our findings suggest that alternative splicing plays a central role in regulating selective extracellular interactions through the neuroligin-neurexin complex at glutamatergic and GABAergic synapses.
Chih
Ben
B
Department of Physiology & Cellular Biophysics, Center for Neurobiology and Behavior, Columbia University Medical Center, College of Physicians & Surgeons, P&S 11-511, 630 West 168th Street, New York, New York 10032, USA.
Gollan
Leora
L
Scheiffele
Peter
P
D017398:Alternative Splicing / Q000502:physiology*; D000818:Animals; D019556:COS Cells; D015816:Cell Adhesion Molecules, Neuronal; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D013569:Synapses / Q000235:genetics* / Q000378:metabolism*
D015816:Cell Adhesion Molecules, Neuronal; D006023:Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C112162:neurexophilin; C093438:neuroligin 1; C098003:neuroligin 2; C086959:neurexin Ibeta