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(Alpha)3(beta)1 integrin regulates epithelial cytoskeletal organization.
Z Wang1, J M Symons, S L Goldstein
1Department of Medicine, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Journal of Cell Science
|August 13, 1999
Summary
Integrins are essential for epithelial cells to form their characteristic sub-cortical cytoskeleton, a function independent of cadherins. This study reveals integrins are critical for cytoskeletal organization and cell junction stability.
Area of Science:
- Cell Biology
- Biochemistry
- Integrative Biology
Background:
- Epithelial cell morphology relies on cell-cell and cell-matrix interactions mediated by integrins and cadherins.
- The specific roles of integrins versus cadherins in maintaining the epithelial sub-cortical cytoskeleton are not well understood.
- Previous studies using integrin-blocking antibodies obscured distinct contributions due to simultaneous loss of cell adhesion and cytoskeletal organization.
Purpose of the Study:
- To investigate the distinct roles of integrins and cadherins in epithelial cell morphology and cytoskeletal organization.
- To elucidate the contribution of alpha3beta1 integrin to the sub-cortical cytoskeleton in kidney collecting duct epithelial cells.
- To determine the cross-regulatory relationship between integrins and cadherins in establishing epithelial cell structure.
Main Methods:
- Utilized alpha3beta1 integrin-deficient mice to isolate and culture kidney collecting duct cells.
- Established immortalized cell lines from wild-type and alpha3beta1 integrin-deficient kidney collecting ducts.
- Analyzed cell morphology, cytoskeletal organization (actin stress fibers, sub-cortical cytoskeleton), and cadherin:catenin complex association with alpha-actinin.
Main Results:
- Alpha3beta1 integrin-deficient cells maintained cadherin-mediated cell-cell adhesions but lacked the sub-cortical cytoskeleton, instead forming actin stress fibers.
- Cell-cell junctions in mutant cells were irregular, unlike the uniform orientation in wild-type cells.
- The association of the cadherin:catenin complex with alpha-actinin was significantly reduced in integrin-deficient cells, indicating impaired cytoskeletal linkage.
Conclusions:
- Integrins play a primary and essential role in establishing and maintaining the epithelial sub-cortical cytoskeleton.
- Integrin-mediated cytoskeletal assembly is crucial for the subsequent association of the cytoskeleton with the cadherin:catenin complex.
- Demonstrated direct evidence of integrin:cadherin cross-regulation, where cadherin function is dependent on integrin presence.