RhoA enhances store-operated Ca entry and intestinal epithelial restitution by interacting with TRPC1 after wounding

نویسندگان

  • Hee Kyoung Chung
  • Navneeta Rathor
  • Shelley R. Wang
  • Jian-Ying Wang
  • Jaladanki N. Rao
چکیده

Chung HK, Rathor N, Wang SR, Wang JY, Rao JN. RhoA enhances store-operated Ca entry and intestinal epithelial restitution by interacting with TRPC1 after wounding. Am J Physiol Gastrointest Liver Physiol 309: G759–G767, 2015. First published September 3, 2015; doi:10.1152/ajpgi.00185.2015.—Early mucosal restitution occurs as a consequence of epithelial cell migration to resealing of superficial wounds after injury. Our previous studies show that canonical transient receptor potential-1 (TRPC1) functions as a store-operated Ca channel (SOC) in intestinal epithelial cells (IECs) and plays an important role in early epithelial restitution by increasing Ca influx. Here we further reported that RhoA, a small GTP-binding protein, interacts with and regulates TRPC1, thus enhancing SOC-mediated Ca entry (SOCE) and epithelial restitution after wounding. RhoA physically associated with TRPC1 and formed the RhoA/TRPC1 complexes, and this interaction increased in stable TRPC1-transfected IEC-6 cells (IEC-TRPC1). Inactivation of RhoA by treating IEC-TRPC1 cells with exoenzyme C3 transferase (C3) or ectopic expression of dominant negative RhoA (DNMRhoA) reduced RhoA/TRPC1 complexes and inhibited Ca influx after store depletion, which was paralleled by an inhibition of cell migration over the wounded area. In contrast, ectopic expression of wild-type (WT)RhoA increased the levels of RhoA/TRPC1 complexes, induced Ca influx through activation of SOCE, and promoted cell migration after wounding. TRPC1 silencing by transfecting stable WT RhoA-transfected cells with siRNA targeting TRPC1 (siTRPC1) reduced SOCE and repressed epithelial restitution. Moreover, ectopic overexpression of WT-RhoA in polyamine-deficient cells rescued the inhibition of Ca influx and cell migration induced by polyamine depletion. These findings indicate that RhoA interacts with and activates TRPC1 and thus stimulates rapid epithelial restitution after injury by inducing Ca signaling.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

RhoA enhances store-operated Ca2+ entry and intestinal epithelial restitution by interacting with TRPC1 after wounding.

Early mucosal restitution occurs as a consequence of epithelial cell migration to resealing of superficial wounds after injury. Our previous studies show that canonical transient receptor potential-1 (TRPC1) functions as a store-operated Ca(2+) channel (SOC) in intestinal epithelial cells (IECs) and plays an important role in early epithelial restitution by increasing Ca(2+) influx. Here we fur...

متن کامل

Caveolin‐1 enhances rapid mucosal restitution by activating TRPC1‐mediated Ca2+ signaling

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 (TRPC1) functions as a store-operated Ca(2+) channel (SOCs) in intestinal epithelial cells (IECs) and regulates epithelial restitution after wounding, but th...

متن کامل

TRPC1 functions as a store-operated Ca2+ channel in intestinal epithelial cells and regulates early mucosal restitution after wounding.

An increase in cytosolic free Ca(2+) concentration ([Ca(2+)](cyt)) results from Ca(2+) release from intracellular stores and extracellular Ca(2+) influx through Ca(2+)-permeable ion channels and is crucial for initiating intestinal epithelial restitution to reseal superficial wounds after mucosal injury. Capacitative Ca(2+) entry (CCE) induced by Ca(2+) store depletion represents a major Ca(2+)...

متن کامل

TRPC1 functions as a store-operated Ca channel in intestinal epithelial cells and regulates early mucosal restitution after wounding

Rao, Jaladanki N., Oleksandr Platoshyn, Vera A. Golovina, Lan Liu, Tongtong Zou, Bernard S. Marasa, Douglas J. Turner, Jason X.-J. Yuan, and Jian-Ying Wang. TRPC1 functions as a store-operated Ca channel in intestinal epithelial cells and regulates early mucosal restitution after wounding. Am J Physiol Gastrointest Liver Physiol 290: G782–G792, 2006. First published November 10, 2005; doi:10.11...

متن کامل

STIM1 translocation to the plasma membrane enhances intestinal epithelial restitution by inducing TRPC1-mediated Ca signaling after wounding

Rao JN, Rathor N, Zou T, Liu L, Xiao L, Yu T, Cui Y, Wang JY. STIM1 translocation to the plasma membrane enhances intestinal epithelial restitution by inducing TRPC1-mediated Ca signaling after wounding. Am J Physiol Cell Physiol 299: C579–C588, 2010. First published July 14, 2010; doi:10.1152/ajpcell.00066.2010.—Early epithelial restitution is an important repair modality in the gut mucosa and...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 2015