TRPC1 channels regulate directionality of migrating cells.
Cell migration depends on the generation of structural asymmetry and on different steps: protrusion and adhesion at the front and traction and detachment at the rear part of the cell. The activity of Ca(2+) channels coordinate these steps by arranging intracellular Ca(2+) signals along the axis of movement. Here, we investigated the role of the putative mechanosensitive canonical transient receptor potential channel 1 (TRPC1) in cell migration. We analyzed its function in transformed renal epithelial (Madin-Darby canine kidney-focus) cells with variation of TRPC1 expression. As shown by time lapse video microscopy, TRPC1 knockdown cells have partially lost their polarity and the ability to persistently migrate into a given direction. This failure is linked to the suppression of a local Ca(2+) gradient at the front of migrating TRPC1 knockdown cells, whereas TRPC1 overexpression leads to steeper Ca(2+) gradients. We propose that the Ca(2+) signaling events regulated by TRPC1 within the lamellipodium determine polarity and directed cell migration.
Institute of Physiology II, University of Münster, Robert-Koch-Str. 27b, 48149, Münster, Germany. afabian@uni-muenster.de
A
A
Fabian
T
T
Fortmann
P
P
Dieterich
C
C
Riethmüller
P
P
Schön
S
S
Mally
B
B
Nilius
A
A
Schwab
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D048430:Cell Shape; D048429:Cell Size; D004285:Dogs; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D018715:Microscopy, Video; D010455:Peptides / Q000494:pharmacology; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013111:Spider Venoms / Q000494:pharmacology; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
D036341:Intercellular Signaling Peptides and Proteins; C411249:MTx4 protein, Grammostola spatulata; D010455:Peptides; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D013111:Spider Venoms; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1