Bemben_2015_Proc.Natl.Acad.Sci.U.S.A_112_2551

Reference

Title : Autism-associated mutation inhibits protein kinase C-mediated neuroligin-4X enhancement of excitatory synapses - Bemben_2015_Proc.Natl.Acad.Sci.U.S.A_112_2551
Author(s) : Bemben MA , Nguyen QA , Wang T , Li Y , Nicoll RA , Roche KW
Ref : Proc Natl Acad Sci U S A , 112 :2551 , 2015
Abstract :

Autism spectrum disorders (ASDs) comprise a highly heritable, multifarious group of neurodevelopmental disorders, which are characterized by repetitive behaviors and impairments in social interactions. Point mutations have been identified in X-linked Neuroligin (NLGN) 3 and 4X genes in patients with ASDs and all of these reside in their extracellular domains except for a single point mutation in the cytoplasmic domain of NLGN4X in which an arginine is mutated to a cysteine (R704C). Here we show that endogenous NLGN4X is robustly phosphorylated by protein kinase C (PKC) at T707, and R704C completely eliminates T707 phosphorylation. Endogenous NLGN4X is intensely phosphorylated on T707 upon PKC stimulation in human neurons. Furthermore, a phospho-mimetic mutation at T707 has a profound effect on NLGN4X-mediated excitatory potentiation. Our results now establish an important interplay between a genetic mutation, a key posttranslational modification, and robust synaptic changes, which can provide insights into the synaptic dysfunction of ASDs.

PubMedSearch : Bemben_2015_Proc.Natl.Acad.Sci.U.S.A_112_2551
PubMedID: 25675530

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Citations formats

Bemben MA, Nguyen QA, Wang T, Li Y, Nicoll RA, Roche KW (2015)
Autism-associated mutation inhibits protein kinase C-mediated neuroligin-4X enhancement of excitatory synapses
Proc Natl Acad Sci U S A 112 :2551

Bemben MA, Nguyen QA, Wang T, Li Y, Nicoll RA, Roche KW (2015)
Proc Natl Acad Sci U S A 112 :2551