Fig. 8: Proposed model of a GPER1-PKA-Centrin signaling axis regulating centriole integrity in colon cancer cells.

GPER1 activation triggers Gαs-dependent stimulation of adenylyl cyclase, which converts ATP into cAMP. The tetrameric PKA holoenzyme, composed of regulatory and catalytic subunit dimers, remains sequestered in an inactive state in the absence of cAMP. Upon binding of cAMP to PKA regulatory subunits, the holoenzyme becomes active and is recruited to the interphase centrosome by AKAP450. At the centrosome, PKA dissociates, releasing its catalytic subunits, which are then free to phosphorylate Centrin at the centrioles. In addition to atypical phosphorylation of Centrin outside of mitosis, the centriolar protein becomes enlarged compared to its normal-sized counterparts in centrosome-amplified cells. Moreover, amplified centrioles display structural abnormalities and reduced length, as described in the main text. C, PKA-Cα; CTN centrin PCM, pericentriolar material, R, PKA-Rα.