Functional TRPM7 channels accumulate at the plasma membrane in response to fluid flow.
Many cells are constantly exposed to fluid mechanical forces generated by flowing blood, and wall shear stresses modulate aspects of their structure and function. However, the mechanisms for mechanotransduction of flow are not well understood. Here we report that TRPM7, which is both an ion channel and a functional kinase, is translocated within cells in response to laminar flow. After exposure of cells to physiological values of laminar fluid flow, the number of TRPM7 molecules localized at or near the plasma membrane increased up to 2-fold, in less than 100 seconds. This increase in membrane-localized GFP-TRPM7, as seen by total internal reflection fluorescence microscopy, closely correlated with increases in TRPM7 current. Both endogenous and heterologously expressed TRPM7 was found in tubulovesicular structures that were translocated to the region of the plasma membrane on induction of shear stress. In vascular smooth muscle cells, but not in several types of endothelial cells, fluid flow increased endogenous native TRPM7 current amplitude. We hypothesize that TRPM7 plays a role in pathological response to vessel wall injury.
Oancea
Elena
E
Howard Hughes Medical Institute, Department of Cardiology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA. oancea@enders.tch.harvard.edu
Wolfe
Joshua T
JT
Clapham
David E
DE
D001775:Blood Circulation; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D021381:Protein Transport; D033081:Shear Strength; D013314:Stress, Mechanical; D050053:TRPM Cation Channels / Q000032:analysis / Q000502:physiology*
D050053:TRPM Cation Channels; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human