Abstract
In secretory cells, polarized Ca2+ signals are determined by compartmentalized localization of Ca2+ signaling proteins at the apical pole. STIM1 and the Orai channels are critical components in store‐operated Ca2+ influx. STIM1 also gates the TRPC channels. We asked how cell stimulation affects the localization, recruitment, and function of these proteins in polarized secretory cells. Inhibition of Orai1, STIM1, or deletion of TRPC1 reduces Ca2+ influx and frequency of Ca2+ oscillations. Orai1 localization is restricted to the apical side. Cell stimulation causes polarized recruitment of STIM1 to the apical and lateral regions, thus to regions with and without Orai1. STIM1 shows higher co‐localization with E‐cadherin than does Orai1, while Orai1 showed higher co‐localization with ZO1. TRPC1 is expressed in apical and basolateral regions of the plasma membrane. Co‐IP of STIM1/Orai1/IP3 receptors/TRPCs is enhanced by cell stimulation and disrupted by 2‐APB. The polarized recruitment of these proteins results in preferred Ca2+ entry that is initiated at the apical pole. These results suggest that in addition to Orai1, STIM1 likely regulates other Ca2+ permeable channels, such as the TRPCs.
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