TRPM4 regulates migration of mast cells in mice.
We demonstrate here that the transient receptor potential melastatin subfamily channel, TRPM4, controls migration of bone marrow-derived mast cells (BMMCs), triggered by dinitrophenylated human serum albumin (DNP-HSA) or stem cell factor (SCF). Wild-type BMMCs migrate after stimulation with DNP-HSA or SCF whereas both stimuli do not induce migration in BMMCs derived from TRPM4 knockout mice (trpm4(-/-)). Mast cell migration is a Ca(2+)-dependent process, and TRPM4 likely controls this process by setting the intracellular Ca(2+) level upon cell stimulation. Cell migration depends on filamentous actin (F-actin) rearrangement, since pretreatment with cytochalasin B, an inhibitor of F-actin formation, prevented both DNP-HSA- and SCF-induced migration in wild-type BMMC. Immunocytochemical experiments using fluorescence-conjugated phalloidin demonstrate a reduced level of F-actin formation in DNP-HSA-stimulated BMMCs from trpm4(-/-) mice. Thus, our results suggest that TRPM4 is critically involved in migration of BMMCs by regulation of Ca(2+)-dependent actin cytoskeleton rearrangements.
Shimizu
Takahiro
T
Department of Molecular Cell Biology, Laboratory of Ion Channel Research, KU Leuven, Campus Gasthuisberg, Herestraat 49, bus 802, B-3000 Leuven, Belgium.
Owsianik
Grzegorz
G
Freichel
Marc
M
Flockerzi
Veit
V
Nilius
Bernd
B
Vennekens
Rudi
R
D000199:Actins / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement; D002633:Chemotaxis / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004140:Dinitrophenols / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D012709:Serum Albumin / Q000378:metabolism; D019089:Stem Cell Factor / Q000494:pharmacology; D050053:TRPM Cation Channels / Q000378:metabolism*
D000199:Actins; D000941:Antigens; D004140:Dinitrophenols; D012709:Serum Albumin; D019089:Stem Cell Factor; D050053:TRPM Cation Channels; C476766:TRPM4 protein, mouse; C058064:dinitrophenyl-human serum albumin conjugate; D007073:Immunoglobulin E; D002118:Calcium