Integrins and dystroglycan regulate astrocyte wound healing: The integrin β1 subunit is necessary for process extension and orienting the microtubular network
| Autor: | Huashan Peng, Salvatore Carbonetto, Waris Ali Shah, Paul C. Holland |
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| Rok vydání: | 2008 |
| Předmět: |
Integrins
Integrin Fluorescent Antibody Technique Microtubules Integrin alpha1beta1 Rats Sprague-Dawley Extracellular matrix Cellular and Molecular Neuroscience Developmental Neuroscience Laminin Cell Adhesion medicine Dystroglycan Animals Dystroglycans Cell adhesion Cells Cultured Embryonic Stem Cells Wound Healing biology Integrin beta1 Cell Polarity Cell Differentiation Cell migration Extracellular Matrix Rats Cell biology medicine.anatomical_structure Biochemistry Astrocytes biology.protein Wound healing Subcellular Fractions Astrocyte |
| Zdroj: | Developmental Neurobiology. 68:559-574 |
| ISSN: | 1932-846X 1932-8451 |
| DOI: | 10.1002/dneu.20593 |
| Popis: | Monolayers of astrocytes in culture respond to a scrape wound by orienting towards the wound and extending processes that will repair it. We show here that they also upregulate the expression of extracellular matrix (ECM) proteins, laminin, and chondroitin sulfated proteoglycan, that are deposited in astrocytic scars in vivo. We have previously shown that the major functional ECM receptors on astrocytes are dystroglycan (DG) plus integrins alpha1beta1, alpha5beta1, alpha6beta1, and alphavbeta3. Consistent with this, laminin fragments that activate alpha1beta1 integrin, alpha6beta1 integrin, and DG all contribute to attachment. During astrocyte attachment, or process extension, integrins and DG are found at the leading edge of the lammelipodium, though they change in distribution with the extent of attachment and the alpha and beta subunits of DG can be spatially uncoupled. Functionally, inhibitory antibodies to DG and integrin alpha1beta1 or the RGD peptide all inhibit process extension, showing that ligand engagement of integrins and DG contribute to process extension. Astrocytes differentiated from DG or beta1 null ES cells respond very differently to wounding. The former fail to extend process and cell polarization is disrupted partially. However, beta1 null astrocytes not only fail to extend processes perpendicular to the wound, but cell polarization is completely disrupted and cells migrate randomly into the wound. We conclude that integrins are essential for astrocyte polarity. |
| Databáze: | OpenAIRE |
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