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PMID: 20631248 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

STIM1 translocation to the plasma membrane enhances intestinal epithelial restitution by inducing TRPC1-mediated Ca2+ signaling after wounding.

American journal of physiology. Cell physiology ·Vol. 299 ·No. 3 ·2010-09-00 ·Pages C579-88

Rao JN, Rathor N, Zou T, Liu L, Xiao L, Yu TX, Cui YH, Wang JY

Abstract

Early epithelial restitution is an important repair modality in the gut mucosa and occurs as a consequence of epithelial cell migration. Canonical transient receptor potential-1 (TRPC1) functions as a store-operated Ca2+ channel (SOCs) in intestinal epithelial cells (IECs) and regulates intestinal restitution, but the exact upstream signals initiating TRPC1 activation after mucosal injury remain elusive. Stromal interaction molecule 1 (STIM1) is a single membrane-spanning protein and is recently identified as essential components of SOC activation. The current study was performed to determine whether STIM1 plays a role in the regulation of intestinal epithelial restitution by activating TRPC1 channels. STIM1 translocation to the plasma membrane increased after wounding, which was followed by an increase in IEC migration to reseal wounds. Increased STIM1 levels at the plasma membrane by overexpressing EF-hand mutant STIM1 enhanced Ca2+ influx through SOCs and stimulated IEC migration after wounding. STIM1 interacted with TRPC1 and formed STIM1/TRPC1 complex, whereas inactivation of STIM1 by STIM1 silencing decreased SOC-mediated Ca2+ influx and inhibited epithelial restitution. In cells overexpressing EF-hand mutant STIM1, TRPC1 silencing also decreased STIM1/TRPC1 complex, reduced SOC-mediated Ca2+ influx, and repressed cell migration after wounding. Our findings demonstrate that induced STIM1 translocation to the plasma membrane promotes IEC migration after wounding by enhancing TRPC1-mediated Ca2+ signaling and provide new insight into the mechanism of intestinal epithelial restitution.

MeSH Terms
Animals Calcium/metabolism Calcium Channels/physiology Calcium Signaling Cell Line Cell Membrane/metabolism Cell Movement Drosophila Proteins/genetics,metabolism Epithelial Cells/physiology Intestinal Mucosa/cytology,injuries,physiology Membrane Proteins/genetics,metabolism Protein Transport Rats Stromal Interaction Molecule 1 TRPC Cation Channels/physiology Wound Healing
Chemicals
Calcium Channels Drosophila Proteins Membrane Proteins Stim protein, Drosophila Stromal Interaction Molecule 1 TRPC Cation Channels transient receptor potential cation channel, subfamily C, member 1 Calcium
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Rao Jaladanki N
Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Rathor Navneeta
Zou Tongtong
Liu Lan
Xiao Lan
Yu Ting-Xi
Cui Yu-Hong
Wang Jian-Ying
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Article Info
Journal
American journal of physiology. Cell physiology
Abbr.
Am J Physiol Cell Physiol
ISSN
1522-1563
DOI
10.1152/ajpcell.00066.2010
Published
2010-09-00
Epub
2010-00-14
Pages
C579-88
Language
English
Region
United States
NLM ID
100901225
PMCID
PMC2944314
Subset
IM
Grants
NIDDK NIH HHS · DK-57819 · United States
NIDDK NIH HHS · DK-61972 · United States
NIDDK NIH HHS · DK-68491 · United States
External Links
PubMed source DOI: 10.1152/ajpcell.00066.2010 PMC Full Text View journal details
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