5-Hydroxytryptamine 6 Receptor (5-HT₆R)-Mediated Morphological Changes via RhoA-Dependent Pathways

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• The serotonin 6 receptor (5-HT₆R) is exclusively expressed in the brain, making it a potential therapeutic target.
• The precise mechanisms linking 5-HT₆R to brain functions are not well understood.

Purpose of the Study:

• To investigate the role of 5-HT₆R in regulating cell morphology.
• To elucidate the downstream signaling pathways involved in 5-HT₆R-mediated cellular effects.

Main Methods:

• Immunocytochemistry
• Western blot analysis
• Live-cell imaging assays
• HEK293 cell line and primary hippocampal neurons

Main Results:

• Activation of 5-HT₆R led to significant cell morphological changes and increased cell surface area in HEK293 cells.
• 5-HT treatment specifically enhanced RhoA-GTP activity, without affecting Rac1 or Cdc42.
• In hippocampal neurons, 5-HT₆R activation increased dendritic protrusion density and size, correlating with RhoA-GTP activation.
• These effects were reversed by a selective 5-HT₆R antagonist (SB258585).

Conclusions:

• 5-HT₆R activation regulates cell morphology via a RhoA-dependent pathway.
• This mechanism is conserved in both mammalian cell lines and primary neurons.
• Findings provide insights into the functional role of 5-HT₆R in neuronal structure.