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Recent advances in the field have elucidated the molecular pathways that underlie these events and have revealed several points of intersection. <jats:styled-content style=\"fixed-case\"><jats:roman>Ca<\/jats:roman><\/jats:styled-content><jats:sup>2+<\/jats:sup> signaling can be divided into two phases: initial events leading to release of <jats:styled-content style=\"fixed-case\"><jats:roman>Ca<\/jats:roman><\/jats:styled-content><jats:sup>2+<\/jats:sup> from endoplasmic reticulum stores, and a second phase involving <jats:styled-content style=\"fixed-case\">STIM<\/jats:styled-content> 1 (stromal interaction molecule 1) clustering and <jats:styled-content style=\"fixed-case\">CRAC<\/jats:styled-content> (calcium release activated calcium) channel activation. Cytoskeletal dynamics promote both phases. During the first phase, the actin cytoskeleton promotes mechanotransduction and serves as a dynamic scaffold for microcluster assembly. Proteins that drive actin polymerization such as <jats:styled-content style=\"fixed-case\">WAS<\/jats:styled-content>p (Wiskott\u2013Aldrich syndrome protein) and <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>1 (hematopoietic lineage cell\u2010specific protein 1) promote signaling through <jats:styled-content style=\"fixed-case\">PLC<\/jats:styled-content>\u03b31 (phospholipase C\u03b31) and release of <jats:styled-content style=\"fixed-case\"><jats:roman>Ca<\/jats:roman><\/jats:styled-content><jats:sup>2+<\/jats:sup> from endoplasmic reticulum stores. During the second phase, the <jats:styled-content style=\"fixed-case\">WAVE<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">WASP<\/jats:styled-content>\u2010family verprolin homologous protein) complex and the microtubule cytoskeleton promote <jats:styled-content style=\"fixed-case\">STIM<\/jats:styled-content> 1 clustering at sites of plasma membrane apposition, opening Orai channels. In addition, gross cell shape changes and organelle movements buffer local <jats:styled-content style=\"fixed-case\"><jats:roman>Ca<\/jats:roman><\/jats:styled-content><jats:sup>2+<\/jats:sup> levels, leading to sustained <jats:styled-content style=\"fixed-case\"><jats:roman>Ca<\/jats:roman><\/jats:styled-content><jats:sup>2+<\/jats:sup> mobilization. Conversely, elevated intracellular <jats:styled-content style=\"fixed-case\"><jats:roman>Ca<\/jats:roman><\/jats:styled-content><jats:sup>2+<\/jats:sup> activates cytoskeletal remodeling. This can occur indirectly, via calpain activity, and directly, via <jats:styled-content style=\"fixed-case\"><jats:roman>Ca<\/jats:roman><\/jats:styled-content><jats:sup>2+<\/jats:sup>\u2010dependent cytoskeletal regulatory proteins such as myosin <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> and L\u2010plastin. While it is true that the cytoskeleton regulates <jats:styled-content style=\"fixed-case\"><jats:roman>Ca<\/jats:roman><\/jats:styled-content><jats:sup>2+<\/jats:sup> responses and <jats:italic>vice versa<\/jats:italic>, interdependence between <jats:styled-content style=\"fixed-case\"><jats:roman>Ca<\/jats:roman><\/jats:styled-content><jats:sup>2+<\/jats:sup> and the cytoskeleton also encompasses signaling events that occur in parallel, downstream of shared intermediates. Inositol cleavage by <jats:styled-content style=\"fixed-case\">PLC<\/jats:styled-content>\u03b31 simultaneously triggers both endoplasmic reticulum store release and diacylglycerol\u2010dependent microtubule organizing center reorientation, while depleting the pool of phosphatidylinositol\u20104,5\u2010bisphosphate, an activator of multiple actin\u2010regulatory proteins. The close interdependence of <jats:styled-content style=\"fixed-case\"><jats:roman>Ca<\/jats:roman><\/jats:styled-content><jats:sup>2+<\/jats:sup> signaling and cytoskeletal dynamics in T cells provides positive feedback mechanisms for T\u2010cell activation and allows for finely tuned responses to extracellular cues.<\/jats:p>","DOI":"10.1111\/imr.12123","type":"journal-article","created":{"date-parts":[[2014,8,30]],"date-time":"2014-08-30T07:27:21Z","timestamp":1409383641000},"page":"80-94","source":"Crossref","is-referenced-by-count":85,"title":["Coordinate control of cytoskeletal remodeling and calcium mobilization during T\u2010cell activation"],"prefix":"10.1111","volume":"256","author":[{"given":"Alexander","family":"Babich","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania Philadelphia PA 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