title: Interaction between CHL1 and serotonin receptor 2c regulates signal transduction and behavior in mice.
abstract: The serotonergic system plays important roles in multiple functions of the nervous system and its malfunctioning leads to neurological and psychiatric disorders. Here, we show that the cell adhesion molecule close homolog of L1 (CHL1), which has been linked to mental disorders, binds to a peptide stretch in the third intracellular loop of the serotonin 2c (5-HT2c) receptor through its intracellular domain. Moreover, we provide evidence that CHL1 deficiency in mice leads to 5-HT2c-receptor-related reduction in locomotor activity and reactivity to novelty, and that CHL1 regulates signaling pathways triggered by constitutively active isoforms of the 5-HT2c receptor. Furthermore, we found that the 5-HT2c receptor and CHL1 colocalize in striatal and hippocampal GABAergic neurons, and that 5-HT2c receptor phosphorylation and its association with phosphatase and tensin homolog (PTEN) and β-arrestin 2 is regulated by CHL1. Our results demonstrate that CHL1 regulates signal transduction pathways through constitutively active 5-HT2c receptor isoforms, thereby altering 5-HT2c receptor functions and implicating CHL1 as a new modulator of the serotonergic system.
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, Hamburg 20246, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Kleene
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, Hamburg 20246, Germany.
authors.forename: Harshita
authors.initials: H
authors.lastname: Chaudhary
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, Hamburg 20246, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Karl
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, Hamburg 20246, Germany.
authors.forename: Jelena
authors.initials: J
authors.lastname: Katic
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, Hamburg 20246, Germany.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kotarska
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, Hamburg 20246, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Guitart
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, Hamburg 20246, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Loers
authors.affiliation: Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Road, Piscataway, NJ 08854, USA Center for Neuroscience, Shantou University Medical College, 22 Xin Ling Road, Shantou, Guangdong 515041, China schachner@stu.edu.cn.
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism; D059330:GABAergic Neurons / Q000166:cytology / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D015815:Cell Adhesion Molecules; C490649:Chl1 protein, mouse; D044405:Receptor, Serotonin, 5-HT2C
keywords: 5-HT2c receptor; CHL1; Exploratory behavior; Signal transduction