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

Soon Hee Kim, Dong Hyuk Kim, Kang Ho Lee, Sun Kyoung Im, Eun Mi Hur, Kwang Chul Chung, Hyewhon Rhim

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Article numbere91402
JournalPLoS One
Volume9
Issue number3
DOIs
Publication statusPublished - 2014 Apr 10

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microtubules
brain
Light
receptors
eating disorders
endocytosis
protein subunits
Alzheimer disease
emotions
serotonin
linkage (genetics)
signal transduction
proteins
yeasts
drugs
Brain
Serotonin
assays
Signal transduction
Microtubule-Associated Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Kim, Soon Hee ; Kim, Dong Hyuk ; Lee, Kang Ho ; Im, Sun Kyoung ; Hur, Eun Mi ; Chung, Kwang Chul ; Rhim, Hyewhon. / Direct interaction and functional coupling between human 5-HT6 receptor and the light chain 1 subunit of the microtubule-associated protein 1B (MAP1B-LC1). In: PLoS One. 2014 ; Vol. 9, No. 3.
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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). / Kim, Soon Hee; Kim, Dong Hyuk; Lee, Kang Ho; Im, Sun Kyoung; Hur, Eun Mi; Chung, Kwang Chul; Rhim, Hyewhon.

In: PLoS One, Vol. 9, No. 3, e91402, 10.04.2014.

Research output: Contribution to journalArticle

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