AUTHOR=Zuko Amila , Oguro-Ando Asami , Post Harm , Taggenbrock Renske L. R. E. , van Dijk Roland E. , Altelaar A. F. Maarten , Heck Albert J. R. , Petrenko Alexander G. , van der Zwaag Bert , Shimoda Yasushi , Pasterkamp R. Jeroen , Burbach J. Peter H. TITLE=Association of Cell Adhesion Molecules Contactin-6 and Latrophilin-1 Regulates Neuronal Apoptosis JOURNAL=Frontiers in Molecular Neuroscience VOLUME=Volume 9 - 2016 YEAR=2016 URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2016.00143 DOI=10.3389/fnmol.2016.00143 ISSN=1662-5099 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.