title: Molecular mechanisms of spontaneous and directed mast cell motility.
abstract: Migration is a fundamental function of immune cells, and a role for Ca(2+) in immune cell migration has been an interest of scientific investigations for many decades. Mast cells are the major effector cells in IgE-mediated immune responses, and cross-linking of IgE-FcεRI complexes at the mast cell surface by antigen activates a signaling cascade that causes mast cell activation, resulting in Ca(2+) mobilization and granule exocytosis. These cells are known to accumulate at sites of inflammation in response to parasite and bacterial infections. Using real-time imaging, we monitored chemotactic migration of RBL and rat BMMCs in response to a gradient of soluble multivalent antigen. Here, we show that Ca(2+) influx via Orai1 plays an important role in regulating spontaneous motility and directional migration of mast cells toward antigen via IgER complexes. Inhibition of Ca(2+) influx or knockdown of the Ca(2+) entry channel protein Orai1 by shRNA causes inhibition of both of these processes. In addition, a mutant Syk- shows impaired spontaneous motility and chemotaxis toward antigen that is rescued by expression of Syk. Our findings identify a novel Ca(2+) influx-mediated, Orai1-dependent mechanism for mast cell migration.
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14850, USA.
authors.forename: Jinmin
authors.initials: J
authors.lastname: Lee
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Veatch
authors.forename: Barbara
authors.initials: B
authors.lastname: Baird
authors.forename: David
authors.initials: D
authors.lastname: Holowka
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D008407:Mast Cells / Q000378:metabolism*; D000071740:ORAI1 Protein; D051381:Rats
chemical_list: D015220:Calcium Channels; D000071740:ORAI1 Protein; C532493:Orai1 protein, rat; D002118:Calcium