On the move, lysosomal CAX drives Ca2+ transport and motility

Abstract

Acidic Ca(2+)stores are important sources of Ca(2+)during cell signaling but little is known about how Ca(2+)enters these stores. In this issue, Melchionda et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201510019) identify a Ca(2+)/H(+)exchanger (CAX) that is required for Ca(2+)uptake and cell migration in vertebrates.

Figure 1.

Lysosomal Ca²⁺ transporters and channels. Our current understanding of lysosomal Ca²⁺ transport and the proteins that regulate the transport of Ca²⁺ into and out of the lysosome is heavily stacked in favor of Ca²⁺ release channels. To date, voltage-gated (CaV2.1/CACNA1A), ligand-gated (TRPML1 and TRPM2), and nucleotide-gated (TPC1, TPC2, and P2X4) channels have all been identified or implicated in lysosomal Ca²⁺ release (Patel and Cai, 2015). Much less is known about the mechanisms of Ca²⁺ entry into lysosomes. In lower order organisms, CAX mediates lysosomal Ca²⁺ entry against the proton gradient. In this issue, Melchionda et al. (2016) provide the first evidence for a mammalian lysosomal Ca²⁺ uptake mechanism in nonplacental mammals. These findings provide further support for the key role of the lysosome as an intracellular Ca²⁺ store.