title: Direct interaction and functional coupling between human 5-HT6 receptor and the light chain 1 subunit of the microtubule-associated protein 1B (MAP1B-LC1).
abstract: Serotonin (5-HT) receptors of type 6 (5-HT6R) play important roles in mood, psychosis, and eating disorders. Recently, a growing number of studies support the use of 5-HT6R-targeting compounds as promising drug candidates for treating cognitive dysfunction associated with Alzheimer's disease. However, the mechanistic linkage between 5-HT6R and such functions remains poorly understood. By using yeast two-hybrid, GST pull-down, and co-immunoprecipitation assays, here we show that human 5-HT6R interacts with the light chain 1 (LC1) subunit of MAP1B protein (MAP1B-LC1), a classical microtubule-associated protein highly expressed in the brain. Functionally, we have found that expression of MAP1B-LC1 regulates serotonin signaling in a receptor subtype-specific manner, specifically controlling the activities of 5-HT6R, but not those of 5-HT4R and 5-HT7R. In addition, we have demonstrated that MAP1B-LC1 increases the surface expression of 5-HT6R and decreases its endocytosis, suggesting that MAP1B-LC1 is involved in the desensitization and trafficking of 5-HT6R via a direct interaction. Together, we suggest that signal transduction pathways downstream of 5-HT6R are regulated by MAP1B, which might play a role in 5-HT6R-mediated signaling in the brain.
authors.affiliation: Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Soon-Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Dong Hyuk
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology, Seoul, Korea; Department of Neuroscience, University of Science and Technology, Daejeon, Korea.
authors.forename: Kang Ho
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Sun-Kyoung
authors.initials: SK
authors.lastname: Im
authors.affiliation: Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Hur
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Kwang Chul
authors.initials: KC
authors.lastname: Chung
authors.affiliation: Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology, Seoul, Korea; Department of Neuroscience, University of Science and Technology, Daejeon, Korea.
authors.forename: Hyewhon
authors.initials: H
authors.lastname: Rhim
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D008024:Ligands; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008024:Ligands; D008869:Microtubule-Associated Proteins; D021122:Protein Subunits; D011985:Receptors, Serotonin; C085284:microtubule-associated protein 1B; C097216:serotonin 6 receptor; D048049:Extracellular Signal-Regulated MAP Kinases