TRPC1 contributes to the Ca2{+}-dependent regulation of adenylyl cyclases

Store-operated Ca2+ entry (SOCE) is mediated via specific plasma membrane channels in response to endoplasmic reticulum (ER) Ca2+ store depletion. This route of Ca2+ entry is central to the dynamic interplay between Ca2+ and cAMP signalling in regulating the activity of Ca2+-sensitive adenylyl cyclase isoforms (AC1/5/6/8). Two proteins have been identified as key components of SOCE: stromal interacting molecule 1 (STIM1) which senses ER Ca2+ store content and translocates to the plasma membrane upon store depletion, where it activates Orai1, the pore-forming component of the Ca2+ release-activated Ca2+ (CRAC) channel. Previous studies reported that co-expression of STIM1 and Orai1 in HEK293 cells enhances Ca2+-stimulated AC8 activity and that AC8 and Orai1 directly interact to enhance this regulation. Nonetheless, the additional involvement of canonical transient receptor potential (TRPC) channels in SOCE has also been proposed. Here, we evaluate the contribution of TRPC1 to SOCE-mediated regulation of Ca2+-sensitive ACs in HEK293 cells stably expressing AC8 (HEK-AC8) and human submandibular gland (HSG) cells expressing an endogenous Ca2+-inhibited AC6. We demonstrate a role for TRPC1 as an integral component of SOCE, alongside STIM1 and Orai1, in regulating Ca2+ fluxes within AC microdomains and influencing cAMP production.

Source: BJ Cell - August 18, 2014 Category: Biochemistry Authors: D Willoughby, H Ong, L Brito de Souza, S Wachten, I S. Ambudkar, D M.F. Cooper Tags: BJ Signal Source Type: research