Frontiers in Molecular Neuroscience (Dec 2016)

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

  • Amila Zuko,
  • Amila Zuko,
  • Asami Oguro-Ando,
  • Asami Oguro-Ando,
  • Harm Post,
  • Harm Post,
  • Renske L.R.E. Taggenbrock,
  • Roland E. van Dijk,
  • Maarten Altelaar,
  • Maarten Altelaar,
  • Albert J R Heck,
  • Albert J R Heck,
  • Alexander G Petrenko,
  • Bert van der Zwaag,
  • Yasushi Shimoda,
  • R. Jeroen Pasterkamp,
  • J. Peter H. Burbach

DOI
https://doi.org/10.3389/fnmol.2016.00143
Journal volume & issue
Vol. 9

Abstract

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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 (ASD) 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.

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