Cell motility is a complex cellular event that involves reorganization of cytoskeleton. This reorganization encompasses the transient polarization of the cell to facilitate the plasma membrane ruffling, a rearrangement of cortical actin cytoskeleton required for the development of cellular protrusions. It is known that extracellular Ca2+ influx is essential for cell migration and for the positive-feedback cycle that maintains leading-edge structures and ruffling activity. The aim of this review is to summarize our knowledge regarding the Ca2+-dependent signaling pathways, Ca2+ transporters and sensors involved in cell migration. Also, we show here reported evidences that support for a crosstalk between Ca2+ transport and the reorganization of the cytoskeleton required for cell migration. In this regard, we will analyze the role of store-operated Ca2+ entry (SOCE) as a modulator of cytoskeleton and cell migration, but also the modulation of this Ca2+ entry pathway by microtubules and the actin cytoskeleton. As a main conclusion, this review will show that data reported in the last years support a role for SOCE in shaping cytoskeleton, but at the same time, SOCE is strongly dependent on cytoskeletal proteins, in an interesting interplay between cytoskeleton and Ca2+ dynamics.
Part of the book: Cytoskeleton
STIM1 and ORAI1 proteins are regulators of intracellular Ca2+ mobilization. This Ca2+ mobilization is essential to shape Ca2+ signaling in eukaryotic cells. STIM1 is a transmembrane protein located at the endoplasmic reticulum, where it acts as an intraluminal Ca2+ sensor. The transient drop of intraluminal Ca2+ concentration triggers STIM1 activation, which relocates to plasma membrane-endoplasmic reticulum junctions to bind and activate ORAI1, a plasma membrane Ca2+ channel. Thus, the Ca2+ influx pathway mediated by STIM1/ORAI1 is termed store-operated Ca2+ entry (SOCE). STIM and ORAI proteins are also involved in non-SOCE Ca2+ influx pathways, as we discuss here. In this chapter, we review the current knowledge regarding the role of SOCE, STIM1, and ORAI1 in cell signaling, with special focus on the modulation of the activity of kinases, phosphatases, and transcription factors that are strongly influenced by the extracellular Ca2+ influx mediated by these regulators.
Part of the book: Calcium and Signal Transduction