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. 2014 Mar 10;9(3):e91402. doi: 10.1371/journal.pone.0091402. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Membrane / metabolism
  • Endocytosis
  • Enzyme Activation
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Immunoprecipitation
  • Ligands
  • Mice
  • Microtubule-Associated Proteins / metabolism*
  • Protein Binding
  • Protein Subunits / metabolism*
  • Receptors, Serotonin / chemistry
  • Receptors, Serotonin / metabolism*

Substances

  • Ligands
  • Microtubule-Associated Proteins
  • Protein Subunits
  • Receptors, Serotonin
  • microtubule-associated protein 1B
  • serotonin 6 receptor
  • Extracellular Signal-Regulated MAP Kinases

Grants and funding

This work was supported by grants from the Pioneer Research Program (No. 2013008915) and Korea Institute of Science and Technology (2E24480), the Republic of Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.