TY - JOUR
T1 - A splice code for trans-synaptic cell adhesion mediated by binding of neuroligin 1 to α- and β-neurexins
AU - Boucard, Antony A.
AU - Chubykin, Alexander A.
AU - Comoletti, Davide
AU - Taylor, Palmer
AU - Südhof, Thomas C.
N1 - Funding Information:
We thank Dr. E. Kavalali (UT Southwestern, Dallas) for advice. This study was supported by a grant from the NIMH (R37 MH52804-08 to T.C.S.), a postdoctoral fellowship from Fonds de la Recherche en Santé du Québec (FRSQ; to A.A.B.), and a grant from Cure Autism Now to D.C.
PY - 2005/10/20
Y1 - 2005/10/20
N2 - Previous studies suggested that postsynaptic neuroligins form a trans-synaptic complex with presynaptic β-neurexins, but not with presynaptic α-neurexins. Unexpectedly, we now find that neuroligins also bind α-neurexins and that α- and β-neurexin binding by neuroligin 1 is regulated by alternative splicing of neuroligin 1 (at splice site B) and of neurexins (at splice site 4). In neuroligin 1, splice site B is a master switch that determines α-neurexin binding but leaves β-neurexin binding largely unaffected, whereas alternative splicing of neurexins modulates neuroligin binding. Moreover, neuroligin 1 splice variants with distinct neurexin binding properties differentially regulate synaptogenesis: neuroligin 1 that binds only β-neurexins potently stimulates synapse formation, whereas neuroligin 1 that binds to both α- and β-neurexins more effectively promotes synapse expansion. These findings suggest that neuroligin binding to α- and β-neurexins mediates trans-synaptic cell adhesion but has distinct effects on synapse formation, indicating that expression of different neuroligin and neurexin isoforms specifies a trans-synaptic signaling code.
AB - Previous studies suggested that postsynaptic neuroligins form a trans-synaptic complex with presynaptic β-neurexins, but not with presynaptic α-neurexins. Unexpectedly, we now find that neuroligins also bind α-neurexins and that α- and β-neurexin binding by neuroligin 1 is regulated by alternative splicing of neuroligin 1 (at splice site B) and of neurexins (at splice site 4). In neuroligin 1, splice site B is a master switch that determines α-neurexin binding but leaves β-neurexin binding largely unaffected, whereas alternative splicing of neurexins modulates neuroligin binding. Moreover, neuroligin 1 splice variants with distinct neurexin binding properties differentially regulate synaptogenesis: neuroligin 1 that binds only β-neurexins potently stimulates synapse formation, whereas neuroligin 1 that binds to both α- and β-neurexins more effectively promotes synapse expansion. These findings suggest that neuroligin binding to α- and β-neurexins mediates trans-synaptic cell adhesion but has distinct effects on synapse formation, indicating that expression of different neuroligin and neurexin isoforms specifies a trans-synaptic signaling code.
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U2 - 10.1016/j.neuron.2005.08.026
DO - 10.1016/j.neuron.2005.08.026
M3 - Article
C2 - 16242404
AN - SCOPUS:26944444692
VL - 48
SP - 229
EP - 236
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 2
ER -