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: Ralf Kleene, Harshita Chaudhary, Nicole Karl, Jelena Katic, Agnieszka Kotarska, Kathrin Guitart, Gabriele Loers, Melitta Schachner
• Journal: Journal of cell science (J Cell Sci) Vol. 128 Issue 24 Pg. 4642-52 (Dec 15 2015) ISSN: 1477-9137 [Electronic] England
• PMID: 26527397 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015. Published by The Company of Biologists Ltd.

Chemical References

• Cell Adhesion Molecules
• Chl1 protein, mouse
• Receptor, Serotonin, 5-HT2C

Topics

• Animals
• Behavior, Animal (physiology)
• Cell Adhesion Molecules (genetics, metabolism)
• Corpus Striatum (cytology, metabolism)
• GABAergic Neurons (cytology, metabolism)
• Hippocampus (cytology, metabolism)
• Mice
• Mice, Knockout
• Receptor, Serotonin, 5-HT2C (genetics, metabolism)
• Signal Transduction (physiology)