The calcium-activated nonselective cation channel TRPM4 is essential for the migration but not the maturation of dendritic cells

Nat Immunol. 2008 Oct;9(10):1148-56. doi: 10.1038/ni.1648. Epub 2008 Aug 31.


Dendritic cell (DC) maturation and migration are events critical for the initiation of immune responses. After encountering pathogens, DCs upregulate the expression of costimulatory molecules and subsequently migrate to secondary lymphoid organs. Calcium (Ca(2+)) entry governs the functions of many hematopoietic cell types, but the role of Ca(2+) entry in DC biology remains unclear. Here we report that the Ca(2+)-activated nonselective cation channel TRPM4 was expressed in and controlled the Ca(2+) homeostasis of mouse DCs. The absence of TRPM4, which elicited Ca(2+) overload, did not influence DC maturation but did considerably impair chemokine-dependent DC migration. Our results establish TRPM4-regulated Ca(2+) homeostasis as crucial for DC mobility but not maturation and emphasize that DC maturation and migration are independently regulated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Calcium Signaling / immunology*
  • Cell Differentiation / immunology*
  • Cell Movement / immunology*
  • Dendritic Cells / cytology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • Gene Expression / immunology
  • Homeostasis / immunology
  • Immunoblotting
  • Mice
  • Mice, Knockout
  • Patch-Clamp Techniques
  • TRPM Cation Channels / genetics
  • TRPM Cation Channels / immunology*
  • TRPM Cation Channels / metabolism


  • TRPM Cation Channels
  • TRPM4 protein, mouse