Kim, Soon-Hee Kim, Dong Hyuk Lee, Kang Ho Im, Sun-Kyoung Hur, Eun-Mi Chung, Kwang Chul Rhim, Hyewhon 2024-01-20T10:04:13Z 2024-01-20T10:04:13Z 2021-09-04 2014-03-10 1932-6203 https://pubs.kist.re.kr/handle/201004/127003 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-HT6(R), 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. English PUBLIC LIBRARY SCIENCE SEROTONIN RECEPTORS MECHANISM CLONING CHANNEL FAMILY TAU Direct Interaction and Functional Coupling between Human 5-HT6 Receptor and the Light Chain 1 Subunit of the Microtubule-Associated Protein 1B (MAP1B-LC1) Article 10.1371/journal.pone.0091402 1 PLOS ONE, v.9, no.3 PLOS ONE 9 3 scie scopus 000332839300120 2-s2.0-84897507885 Multidisciplinary Sciences Science & Technology - Other Topics Article SEROTONIN RECEPTORS MECHANISM CLONING CHANNEL FAMILY TAU