Bidirectional Ca2+ signalling occurs between the endoplasmic reticulum and acidic organelles
Morgan AJ., Galione A., Davis LC., Wagner KTY., Lewis AM., Parrington J., Churchill GC.
The endoplasmic reticulum (ER) and acidic organelles (endo-lysosomes) act as separate Ca2+ stores that release Ca2+ in response to the second messengers IP3 and cADPR (ER) or NAADP (acidic vesicles). Typically, trigger-Ca2+ rleased from acidic organelles by NAADP subsequently recruits IP3 (or ryanodine) receptors on the EF, and anterograde signal important for amplification and Ca2+ 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 Ca2+ released from the ER can activate the NAADP pathway in two ways: first, by stimulating CA2+-dependent NAADP synthesis; second, by activating NAADP-regulated channels. Moreoever, the differential effects of EGTA and BAPTA (slow and fast Ca2+ chelators respectively) suggest that the acidic organelles are preferentially activated by local microdomains of high Ca2+ at junctions between the ER and acidic organelles. Biodirectional organelle communication may have wider implications for endo-lysosomal function as well as the generation of Ca2+ oscillations and waves.