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Direct interaction and functional coupling between human 5-HT6 receptor and the light chain 1 subunit of the microtubule-associated protein 1B (MAP1B-LC1). | LitMetric

Direct interaction and functional coupling between human 5-HT6 receptor and the light chain 1 subunit of the microtubule-associated protein 1B (MAP1B-LC1).

PLoS One

Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology, Seoul, Korea; Department of Neuroscience, University of Science and Technology, Daejeon, Korea.

Published: March 2016

AI Article Synopsis

  • Serotonin type 6 receptors (5-HT6R) are linked to mood, psychosis, and appetite disorders, and have shown promise for treating cognitive issues in Alzheimer's patients.
  • Recent research reveals that 5-HT6R interacts with MAP1B's light chain 1 (MAP1B-LC1), a brain protein that influences serotonin signaling specifically related to 5-HT6R.
  • MAP1B-LC1 boosts the presence of 5-HT6R on the cell surface and reduces its internalization, indicating it plays a key role in how 5-HT6R functions and is transported in brain cells.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3948860PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0091402PLOS

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