Molecular Biology Select

Rapid and local changes in the concentration of calcium ions can have a dramatic impact on signaling pathways and cell behavior. The papers discussed in this Molecular Biology Select reveal insights into the molecular mediators of calcium signaling in diverse biological contexts, including cell migration, mitochondrial movement, neuronal gene expression, and host responses to invading microorganisms. Although numerous proteins involved in cell migration are regulated by calcium ions (Ca 2+), it has been unclear how Ca 2+ dynamics are translated into a migrating cell's decision to turn a particular way in response to guidance cues. According to the recent study by Wei et al. (2008), local and brief bursts of Ca 2+ at the cell's leading edge provide a signal that steers the migrating cells. Using confocal microscopy to collect consecutive images of a moving cell, the authors visualized Ca 2+ concentrations in human embry-onic lung fibroblasts. They show that although the concentration of Ca 2+ is generally lower at the leading edge than at other regions of the migrating cell, periodic bursts of Ca 2+ , called ''calcium flickers,'' do occur at discrete loci at the leading edge. Moreover, when cells are exposed to a gradient of the chemoattractant PDGF (platelet-derived growth factor) the distribution of calcium flickers across the leading edge correlates with the direction of turning. The authors then delve into the basis for the phenomenon and show that calcium flickers are a response to membrane tension and result from the opening of the stretch-activated calcium channel TRPM7. This initial Ca 2+ influx can then be amplified by release of Ca 2+ from intracellular stores in the endoplasmic reticulum. The authors' characterization of calcium flickers might also shed light on why background calcium levels in migrating cells are kept lower at the leading edge than at the trailing edge. Presumably, this low Ca 2+ concentration improves the ratio of signal (the calcium flicker) to noise (background Ca 2+), thereby enhancing the sensitivity of the leading edge to external guidance cues. Future work may also reveal whether calcium flickers are involved in other cellular behaviors in addition to cell migration. When mitochondria sense an increase in Ca 2+ concentration, they halt their movement along microtubules. It has been proposed that this behavior helps to position mitochondria near regions of high energy demand in the cell. Saotome et al. (2008) now show that the GTPases Miro1 and Miro2 regulate …