| Literature DB >> 32243781 |
Thien A Nguyen1, Kunwei Wu2, Saurabh Pandey2, Alexander W Lehr3, Yan Li4, Michael A Bemben3, John D Badger3, Julie L Lauzon5, Tongguang Wang6, Kareem A Zaghloul7, Audrey Thurm8, Mahim Jain9, Wei Lu2, Katherine W Roche10.
Abstract
Autism spectrum disorder (ASD) is more prevalent in males; however, the etiology for this sex bias is not well understood. Many mutations on X-linked cell adhesion molecule NLGN4X result in ASD or intellectual disability. NLGN4X is part of an X-Y pair, with NLGN4Y sharing ∼97% sequence homology. Using biochemistry, electrophysiology, and imaging, we show that NLGN4Y displays severe deficits in maturation, surface expression, and synaptogenesis regulated by one amino acid difference with NLGN4X. Furthermore, we identify a cluster of ASD-associated mutations surrounding the critical amino acid in NLGN4X, and these mutations phenocopy NLGN4Y. We show that NLGN4Y cannot compensate for the functional deficits observed in ASD-associated NLGN4X mutations. Altogether, our data reveal a potential pathogenic mechanism for male bias in NLGN4X-associated ASD. Published by Elsevier Inc.Entities:
Keywords: ASD; ID; X chromosome; Y chromosome; autism; intellectual disability; neuroligin-4X; neuroligin-4Y; sex-bias; synaptic transmission
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Year: 2020 PMID： 32243781 PMCID： PMC7491604 DOI： 10.1016/j.neuron.2020.03.008
Source DB: PubMed Journal: Neuron ISSN： 0896-6273 Impact factor: 17.173