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Front Mol Neurosci. 2016 Dec 15;9:143. doi: 10.3389/fnmol.2016.00143. eCollection 2016.

Association of Cell Adhesion Molecules Contactin-6 and Latrophilin-1 Regulates Neuronal Apoptosis.

Author information

1
Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht Utrecht, Netherlands.
2
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht UniversityUtrecht, Netherlands; Netherlands Proteomics CentreUtrecht, Netherlands.
3
Laboratory of Receptor Cell Biology, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences Moscow, Russia.
4
Department of Genetics, University Medical Center Utrecht Utrecht, Netherlands.
5
Department of Bioengineering, Nagaoka University of Technology Nagaoka, Japan.

Abstract

In view of important neurobiological functions of the cell adhesion molecule contactin-6 (Cntn6) that have emerged from studies on null-mutant mice and autism spectrum disorders patients, we set out to examine pathways underlying functions of Cntn6 using a proteomics approach. We identified the cell adhesion GPCR latrophilin-1 (Lphn1, a.k.a. CIRL1/CL, ADGRL1) as a binding partner for Cntn6 forming together a heteromeric cis-complex. Lphn1 expression in cultured neurons caused reduction in neurite outgrowth and increase in apoptosis, which was rescued by coexpression of Cntn6. In cultured neurons derived from Cntn6-/- mice, Lphn1 knockdown reduced apoptosis, suggesting that the observed apoptosis was Lphn1-dependent. In line with these data, the number of apoptotic cells was increased in the cortex of Cntn6-/- mice compared to wild-type littermate controls. These results show that Cntn6 can modulate the activity of Lphn1 by direct binding and suggests that Cntn6 may prevent apoptosis thereby impinging on neurodevelopment.

KEYWORDS:

ASD; Cntn6; Lphn1; apoptosis; autism; cell adhesion molecules; neurodevelopmental disorders; neuronal outgrowth

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