Open AccessCaveolin‐1 enhances rapid mucosal restitution by activating TRPC 1‐mediated Ca 2+ signaling
Author(s) -
Rathor Navneeta,
Chung Hee K.,
Wang Shelley R.,
Wang JianYing,
Turner Douglas J.,
Rao Jaladanki N.
Publication year - 2014
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.12193
Subject(s) - trpc1 , microbiology and biotechnology , transient receptor potential channel , transfection , orai1 , chemistry , immunoprecipitation , caveolin , signal transduction , stim1 , caveolae , receptor , biology , endoplasmic reticulum , biochemistry , gene
Early rapid mucosal restitution occurs as a consequence of epithelial cell migration to reseal superficial wounds, a process independent of cell proliferation. Our previous studies revealed that the canonical transient receptor potential‐1 ( TRPC 1) functions as a store‐operated Ca 2+ channel ( SOC s) in intestinal epithelial cells ( IEC s) and regulates epithelial restitution after wounding, but the exact mechanism underlying TRPC 1 activation remains elusive. Caveolin‐1 (Cav1) is a major component protein that is associated with caveolar lipid rafts in the plasma membrane and was recently identified as a regulator of store‐operated Ca 2+ entry ( SOCE ). Here, we showed that Cav1 plays an important role in the regulation of mucosal restitution by activating TRPC 1‐mediated Ca 2+ signaling. Target deletion of Cav1 delayed gastric mucosal repair after exposure to hypertonic NaCl in mice, although it did not affect total levels of TRPC 1 protein. In cultured IEC s , Cav1 directly interacted with TRPC 1 and formed Cav1/ TRPC 1 complex as measured by immunoprecipitation assays. Cav1 silencing in stable TRPC 1‐transfected cells by transfection with siCav1 reduced SOCE without effect on the level of resting [Ca 2+ ] cyt . Inhibition of Cav1 expression by siCav1 and subsequent decrease in Ca 2+ influx repressed epithelial restitution, as indicated by a decrease in cell migration over the wounded area, whereas stable ectopic overexpression of Cav1 increased Cav1/ TRPC 1 complex, induced SOCE , and enhanced cell migration after wounding. These results indicate that Cav1 physically interacts with and activates TRPC 1, thus stimulating TRPC 1‐mediated Ca 2+ signaling and rapid mucosal restitution after injury.