Coupling acidic organelles with the ER through Ca2+ microdomains at membrane contact sites

Acidic organelles such as lysosomes serve as non-canonical Ca2+ stores. The Ca2+ mobilising messenger NAADP is thought to trigger local Ca2+ release from such stores. These events are then amplified by Ca2+ channels on canonical ER Ca2+ stores to generate physiologically relevant global Ca2+ signals. Coupling likely occurs at microdomains formed at membrane contact sites between acidic organelles and the ER. Molecular analyses and computational modelling suggest heterogeneity in the composition of these contacts and predicted Ca2+ microdomain behaviour. Conversely, acidic organelles might also locally amplify and temper ER-evoked Ca2+ signals. Ca2+ microdomains between distinct Ca2+ stores are thus likely to be integral to the genesis of complex Ca2+ signals. (C) 2015 Elsevier Ltd. All rights reserved.