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Journal of Molecular Neuroscience

, Volume 56, Issue 1, pp 89–101 | Cite as

Novel Interactive Partners of Neuroligin 3: New Aspects for Pathogenesis of Autism

  • Chen Shen
  • Li-rong Huo
  • Xin-liang Zhao
  • Pei-rong Wang
  • Nanbert Zhong
Article

Abstract

Autism is a neurodevelopmental disorder with a strong genetic predisposition. Neurolign 3 (NLGN3) as a postsynaptic transmembrane protein, functions in both neuron synaptogenesis and glia-neuron communications. Previously, a gain of function mutation (R451C) in NLGN3 was identified in autistic patients, which illustrates the involvement of NLGN3 in autism pathogenesis. As proper synaptic targeting and functioning are controlled by intracellular protein interactions, in the current study, we tried to discover the intracellular regulation network in which NLGN3 might be involved by a yeast two-hybrid-based interactor identification. Fifty-one protein candidate partners were identified after screening a human fetal complementary DNA (cDNA) library with an intracellular fragment of NLGN3. The interactions of NLGN3 with a subset of candidates, including EEF1A1, FLNA, ITPRIP, CYP11A1, MT-CO2, GPR175, ACOT2, and QPRT, were further validated in human neuroblastoma cells or brain tissues. Furthermore, our study suggested that NLGN3 was functioning in cytosolic calcium balance and participating in calcium-regulated cellular processes. Our findings of novel NLGN3 binding partners provide evidences of involvement of NLGN3 in multiple biological pathways, especially calcium regulating and mitochondrial function, thus suggesting further significance. This new data not only leads to a better understanding of the physiological functions of NLGN3, but also provide new aspects for pathogenesis of autism.

Keywords

NLGN3 Yeast two-hybrid Co-immunoprecipitation Protein-protein interaction Co-localization Cytosolic calcium 

Notes

Acknowledgments

This work was supported in part by the “973” project (2012CB517905) of the Chinese Ministry of Sciences and technology, National Nature Science Foundation (30671157, 81301403), the Shanghai Municipal Department of Science and Technology (2009JC1412600), and the New York State Office of Mental Retardation and Developmental Disabilities (NYS OMRDD).

Conflict of Interest

The authors declare that there is no conflict of interests regarding the publication of this article.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Chen Shen
    • 1
    • 2
  • Li-rong Huo
    • 1
    • 3
  • Xin-liang Zhao
    • 1
  • Pei-rong Wang
    • 1
  • Nanbert Zhong
    • 1
    • 4
  1. 1.Peking University Center of Medical GeneticsBeijing 100191China
  2. 2.Key Laboratory of Major Diseases in Children, State Key Discipline of Pediatrics of Ministry of Education, Beijing Pediatric Research Institute and Beijing Children’s HospitalCapital Medical UniversityBeijing 100045China
  3. 3.Department of Neurology, Fu Xing HospitalCapital Medical UniversityBeijingChina
  4. 4.New York State Institute for Basic Research in Developmental DisabilitiesStaten IslandUSA

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