TRPM4 regulates migration of mast cells in mice

Cell Calcium. 2009 Mar;45(3):226-32. doi: 10.1016/j.ceca.2008.10.005. Epub 2008 Nov 28.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Antigens / pharmacology
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Calcium / metabolism
  • Cell Movement*
  • Chemotaxis / drug effects
  • Cytoskeleton / drug effects
  • Cytoskeleton / metabolism
  • Dinitrophenols / metabolism
  • Humans
  • Immunoglobulin E / immunology
  • Mast Cells / cytology*
  • Mast Cells / drug effects
  • Mast Cells / metabolism*
  • Mice
  • Serum Albumin / metabolism
  • Stem Cell Factor / pharmacology
  • TRPM Cation Channels / metabolism*

Substances

  • Actins
  • Antigens
  • Dinitrophenols
  • Serum Albumin
  • Stem Cell Factor
  • TRPM Cation Channels
  • TRPM4 protein, mouse
  • dinitrophenyl-human serum albumin conjugate
  • Immunoglobulin E
  • Calcium