RT Journal Article
SR Electronic
T1 MMP2-9 Cleavage of Dystroglycan Alters the Size and Molecular Composition of Schwann Cell Domains
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 12208
OP 12217
DO 10.1523/JNEUROSCI.0141-11.2011
VO 31
IS 34
A1 Felipe A. Court
A1 Desirée Zambroni
A1 Ernesto Pavoni
A1 Cristina Colombelli
A1 Chiara Baragli
A1 Gianluca Figlia
A1 Lydia Sorokin
A1 William Ching
A1 James L. Salzer
A1 Lawrence Wrabetz
A1 M. Laura Feltri
YR 2011
UL http://www.jneurosci.org/content/31/34/12208.abstract
AB Myelinating glial cells exhibit a spectacular cytoarchitecture, because they polarize on multiple axes and domains. How this occurs is essentially unknown. The dystroglycan–dystrophin complex is required for the function of myelin-forming Schwann cells. Similar to other tissues, the dystroglycan complex in Schwann cells localizes with different dystrophin family members in specific domains, thus promoting polarization. We show here that cleavage of dystroglycan by matrix metalloproteinases 2 and 9, an event that is considered pathological in most tissues, is finely and dynamically regulated in normal nerves and modulates dystroglycan complex composition and the size of Schwann cell compartments. In contrast, in nerves of Dy2j/2j mice, a model of laminin 211 deficiency, metalloproteinases 2 and 9 are increased, causing excessive dystroglycan cleavage and abnormal compartments. Pharmacological inhibition of cleavage rescues the cytoplasmic defects of Dy2j/2j Schwann cells. Thus, regulated cleavage may be a general mechanism to regulate protein complex composition in physiological conditions, whereas unregulated processing is pathogenic and a target for treatment in disease.