Bidirectional Ca²? signaling occurs between the endoplasmic reticulum and acidic organelles.
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ABSTRACT: The endoplasmic reticulum (ER) and acidic organelles (endo-lysosomes) act as separate Ca(2+) stores that release Ca(2+) in response to the second messengers IP3 and cADPR (ER) or NAADP (acidic organelles). Typically, trigger Ca(2+) released from acidic organelles by NAADP subsequently recruits IP3 or ryanodine receptors on the ER, an anterograde signal important for amplification and Ca(2+) oscillations/waves. We therefore investigated whether the ER can signal back to acidic organelles, using organelle pH as a reporter of NAADP action. We show that Ca(2+) released from the ER can activate the NAADP pathway in two ways: first, by stimulating Ca(2+)-dependent NAADP synthesis; second, by activating NAADP-regulated channels. Moreover, the differential effects of EGTA and BAPTA (slow and fast Ca(2+) chelators, respectively) suggest that the acidic organelles are preferentially activated by local microdomains of high Ca(2+) at junctions between the ER and acidic organelles. Bidirectional organelle communication may have wider implications for endo-lysosomal function as well as the generation of Ca(2+) oscillations and waves.
SUBMITTER: Morgan AJ
PROVIDER: S-EPMC3601362 | biostudies-literature | 2013 Mar
REPOSITORIES: biostudies-literature
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