Integrin alpha8beta1 regulates adhesion, migration and proliferation of human intestinal crypt cells via a predominant RhoA/ROCK-dependent mechanism.
BACKGROUND
Integrins are transmembrane alphabeta heterodimer receptors that function as structural and functional bridges between the cytoskeleton and ECM (extracellular matrix) molecules. The RGD (arginine-glycine-aspartate tripeptide motif)-dependent integrin alpha8beta1 has been shown to be involved in various cell functions in neuronal and mesenchymal-derived cell types. Its role in epithelial cells remains unknown.


RESULTS
Integrin alpha8beta1 was found to be expressed in the crypt cell population of the human intestine but was absent from differentiating and mature epithelial cells of the villus. The function of alpha8beta1 in epithelial crypt cells was investigated at the cellular level using normal HIECs (human intestinal epithelial cells). Specific knockdown of alpha8 subunit expression using an shRNA (small-hairpin RNA) approach showed that alpha8beta1 plays important roles in RGD-dependent cell adhesion, migration and proliferation via a RhoA/ROCK (Rho-associated kinase)-dependent mechanism as demonstrated by active RhoA quantification and pharmacological inhibition of ROCK. Moreover, loss of alpha8beta1, through RhoA/ROCK, impairs FA (focal adhesion) complex integrity as demonstrated by faulty vinculin recruitment.


CONCLUSIONS
Integrin alpha8beta1 is expressed in epithelial cells. In intestinal crypt cells, alpha8beta1 is closely involved in the regulation of adhesion, migration and cell proliferation via a predominant RhoA/ROCK-dependent mechanism. These results suggest an important role for this integrin in intestinal crypt cell homoeostasis.
Benoit
Yannick D
YD
CIHR Team on the Digestive Epithelium, Département d'anatomie et biologie cellulaire, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, QC, Canada, J1H 5N4.
Lussier
Carine
C
Ducharme
Pierre-Alexandre
PA
Sivret
Sophie
S
Schnapp
Lynn M
LM
Basora
Nuria
N
Beaulieu
Jean-François
JF
D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D005333:Fetus; D015870:Gene Expression; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D007422:Intestines / Q000166:cytology* / Q000196:embryology; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D016023:Integrins; C094866:integrin alpha8beta1; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein