Integrins and dystroglycan regulate astrocyte wound healing:: The integrin β1 subunit is necessary for process extension and orienting the microtubular network

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 alpha 1 beta 1, alpha 5 beta 1, alpha 6 beta 1, and alpha v beta 3. Consistent with this, laminin fragments that activate alpha 1 beta 1 integrin, alpha 6 beta 1 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 a and P subunits of DG can be spatially uncoupled. Functionally, inhibitory antibodies to DG and integrin alpha 1 beta 1 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 beta 1 null ES cells respond very differently to wounding. The former fail to extend process and cell polarization is disrupted partially. However, beta 1 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. (C) 2008 Wiley Periodicals, Inc.