
TAS2Rs are bitter taste receptors expressed on human airway smooth muscle (HASM) cells, and their activation causes airway relaxation. This relaxation occurs through F-actin severing, which is caused by TAS2R-promoted cofilin dephosphorylation. This dephosphorylation is due to the TAS2R-mediated deactivation of LIM domain kinase, which is inhibited by the polarity protein partitioning defective 3 (Par3). Knock-down of either cofilin or Par3 inhibited TAS2R14 agonist-induced relaxation, and blocking Ca2+ release also inhibited cofilin dephosphorylation, suggesting a role for Ca2+ in actin-modifying pathways. These findings provide insight into the mechanisms underlying TAS2R-mediated HASM relaxation and suggest potential targets for bronchodilators for asthma or chronic obstructive pulmonary disease.
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