Serotonin 2A (5-HT(2A)) receptor affects cell–matrix adhesion and the formation and maintenance of stress fibers in HEK293 cells

5-HT(2A,) a G-protein coupled receptor, is widely expressed in the human body, including in the gastrointestinal tract, platelets and the nervous system. It mediates various functions, for e.g. learning, memory, mood regulation, platelet aggregation and vasoconstriction, but its involvement in cell-adhesion remains largely unknown. Here we report a novel role for 5-HT(2A) in cell–matrix adhesion. In HEK293 cells, which are loosely adherent, expression and stimulation of human or rat 5-HT(2A) receptor by agonists such as serotonin or 2,5-dimethoxy-4-iodoamphetamine (DOI) led to a significant increase in adhesion, while inhibition of 5-HT(2A) by antipsychotics, such as risperidone, olanzapine or chlorpromazine prevented it. 5-HT(2A) activation gave rise to stress fibers in these cells and was also required for their maintenance. Mechanistically, the 5-HT(2A)-mediated adhesion was mediated by downstream PKC and Rho signaling. Since 5-HT(2A) is associated with many disorders such as dementia, depression and schizophrenia, its role in cell–matrix adhesion could have implications for neural circuits.