The trans-golgi compartment: A new distinct intracellular Ca store.

The Golgi apparatus (GA) is an intracellular organelle that plays a central role in lipid and protein posttranslational modification and sorting. In addition, the GA has been also shown to be involved in Ca(2+) signalling, as: (i) it accumulates Ca(2+) within its lumen in an ATP-dependent process catalyzed by two enzymes, the sarco-endoplasmic reticulum Ca(2+) ATPase (SERCA) and the secretory pathway Ca(2+) ATPase1 (SPCA1), and (ii) it releases Ca(2+) during cell stimulation in response to inositol 1,4,5-trisphosphate (IP(3)) receptor activation. Therefore, on this aspect, the GA appears to behave similarly to the major intracellular Ca(2+) store, the endoplasmic reticulum (ER). By using a new FRET-based Ca(2+) probe, specifically targeted to the trans-compartment of the GA, we demonstrate that the organelle is heterogeneous in terms of Ca(2+) handling, the trans-Golgi being insensitive to IP(3) and capable of accumulating Ca(2+) solely through the activity of SPCA1. The SERCA and the IP(3) receptor appear to be restricted to the cis- and intermediate GA compartments. Moreover, selective reduction of Ca(2+) concentration within the trans-Golgi, obtained by reducing the level of SPCA1 by RNAi, results in major alterations of protein trafficking within the secretory pathway and induces the collapse of the entire GA morphology.