PubMed 21120665

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPC , TRPC1

Title: Chemotaxis of MDCK-F cells toward fibroblast growth factor-2 depends on transient receptor potential canonical channel 1.

Authors: Anke Fabian, Thomas Fortmann, Etmar Bulk, Valerie C Bomben, Harald Sontheimer, Albrecht Schwab

Journal, date & volume: Pflugers Arch., 2011 Feb , 461, 295-306

PubMed link:

Movement toward the source of a chemoattractant gradient is a basic cellular property in health and disease. Enhanced migration during metastasis involves deregulated growth factor signaling. Growth factor stimulation and cell migration converge both on the important second messenger Ca(2+). To date, the molecular identification of Ca(2+) entry pathways activated by growth factors during chemotaxis is still an open issue. We investigated the involvement of the nonselective Ca(2+) channel TRPC1 (transient receptor potential canonical 1) in FGF-2 guided chemotaxis by means of time-lapse video microscopy and by functional Ca(2+) measurements. To specifically address TRPC1 function in transformed MDCK cells we altered the expression levels by siRNA or overexpression. We report that TRPC1 channels are required for the orientation of transformed MDCK cells in FGF-2 gradients because TRPC1 knockdown or pharmacological blockade prevented chemotaxis. Stimulation with FGF-2 triggered an immediate Ca(2+) influx via TRPC1 channels that depended on phospholipase C and phosphatidylinositol 3-kinase signaling. Impeding this Ca(2+) influx abolished chemotaxis toward FGF-2. This functional connection correlated with clustering of FGF receptors and TRPC1 channels as was observed by immunolabeling. These findings show the important interplay between growth factor signaling and Ca(2+) influx in chemotaxis.