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

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

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article number143
JournalFrontiers in Molecular Neuroscience [E]
Volume9
DOIs
Publication statusPublished - 2016

Keywords

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

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