title: Interaction proteomics of canonical Caspr2 (CNTNAP2) reveals the presence of two Caspr2 isoforms with overlapping interactomes.
abstract: Autism is a human developmental brain disorder characterized by impaired social interaction and communication. Contactin-associated protein-like 2 (Caspr2, CNTNAP2) is a known genetic risk factor of autism. However, how this protein might contribute to pathology is unclear. In this study, we demonstrate that Caspr2 is abundantly present in lipid raft and in the synaptic membrane but is highly depleted in the postsynaptic density. The Caspr2 protein level in hippocampus is present at a constant level during synapse formation and myelination from P0 to P84. Interaction proteomics revealed the interactors of Caspr2, including CNTN2, KCNAs, members of the ADAM family (ADAM22, ADAM23 and ADAM11), members of LGI family and MAGUKs (DLGs and MPPs). Interestingly, a short form of Caspr2 was detected, which lacks most of the extracellular domains, however, is still associated with ADAM22 and to a lesser extent LGI1 and Kv1 channels. The comprehensive Caspr2 interactome revealed here might aid in understanding the molecular mechanisms underlying autism. This article is part of a Special Issue titled Neuroproteomics: Applications in Neuroscience and Neurology.
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, De Boelelaan 1085, Amsterdam 1081 HV, The Netherlands; Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, De Boelelaan 1085, Amsterdam 1081 HV, The Netherlands.
authors.forename: Ning
authors.initials: N
authors.lastname: Chen
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, De Boelelaan 1085, Amsterdam 1081 HV, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Koopmans
authors.affiliation: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Aaron
authors.initials: A
authors.lastname: Gordon
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, De Boelelaan 1085, Amsterdam 1081 HV, The Netherlands.
authors.forename: Iryna
authors.initials: I
authors.lastname: Paliukhovich
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, De Boelelaan 1085, Amsterdam 1081 HV, The Netherlands.
authors.forename: Remco V
authors.initials: RV
authors.lastname: Klaassen
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, De Boelelaan 1085, Amsterdam 1081 HV, The Netherlands.
authors.forename: Roel C
authors.initials: RC
authors.lastname: van der Schors
authors.affiliation: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Elior
authors.initials: E
authors.lastname: Peles
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, De Boelelaan 1085, Amsterdam 1081 HV, The Netherlands.
authors.forename: Matthijs
authors.initials: M
authors.lastname: Verhage
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, De Boelelaan 1085, Amsterdam 1081 HV, The Netherlands.
authors.forename: August B
authors.initials: AB
authors.lastname: Smit
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, De Boelelaan 1085, Amsterdam 1081 HV, The Netherlands. Electronic address: k.w.li@vu.nl.
authors.forename: Ka Wan
authors.initials: KW
authors.lastname: Li
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D040901:Proteomics
chemical_list: C568163:CNTNAP2 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms
keywords: Autism; Brain; Caspr2; Interaction proteomics; Mouse model