title: Association of Cell Adhesion Molecules Contactin-6 and Latrophilin-1 Regulates Neuronal Apoptosis.
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 heteromericcis-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 fromCntn6-/-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 ofCntn6-/-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.
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht Utrecht, Netherlands.
authors.forename: Amila
authors.initials: A
authors.lastname: Zuko
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht Utrecht, Netherlands.
authors.forename: Asami
authors.initials: A
authors.lastname: Oguro-Ando
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht UniversityUtrecht, Netherlands; Netherlands Proteomics CentreUtrecht, Netherlands.
authors.forename: Harm
authors.initials: H
authors.lastname: Post
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht Utrecht, Netherlands.
authors.forename: Renske L R E
authors.initials: RL
authors.lastname: Taggenbrock
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht Utrecht, Netherlands.
authors.forename: Roland E
authors.initials: RE
authors.lastname: van Dijk
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht UniversityUtrecht, Netherlands; Netherlands Proteomics CentreUtrecht, Netherlands.
authors.forename: A F Maarten
authors.initials: AF
authors.lastname: Altelaar
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht UniversityUtrecht, Netherlands; Netherlands Proteomics CentreUtrecht, Netherlands.
authors.forename: Albert J R
authors.initials: AJ
authors.lastname: Heck
authors.affiliation: Laboratory of Receptor Cell Biology, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences Moscow, Russia.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Petrenko
authors.affiliation: Department of Genetics, University Medical Center Utrecht Utrecht, Netherlands.
authors.forename: Bert
authors.initials: B
authors.lastname: van der Zwaag
authors.affiliation: Department of Bioengineering, Nagaoka University of Technology Nagaoka, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shimoda
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht Utrecht, Netherlands.
authors.forename: R J
authors.initials: RJ
authors.lastname: Pasterkamp
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht Utrecht, Netherlands.
authors.forename: J P H
authors.initials: JP
authors.lastname: Burbach
keywords: ASD; Cntn6; Lphn1; apoptosis; autism; cell adhesion molecules; neurodevelopmental disorders; neuronal outgrowth