title: Effect of beta-dystroglycan processing on utrophin/Dp116 anchorage in normal and mdx mouse Schwann cell membrane.
abstract: In the peripheral nervous system, utrophin and the short dystrophin isoform (Dp116) are co-localized at the outermost layer of the myelin sheath of nerve fibers; together with the dystroglycan complex. Dp116 is associated with multiple glycoproteins, i.e. sarcoglycans, and alpha- and beta-dystroglycan, which anchor the cytoplasmic protein subcomplex to the extracellular basal lamina. In peripheral nerve, matrix metalloproteinase activity disrupts the dystroglycan complex by cleaving the extracellular domain of beta-dystroglycan. Metalloproteinase creates a 30 kDa fragment of beta-dystroglycan, leading to a disruption of the link between the extracellular matrix and the cell membrane. Here we asked if the processing of the beta-dystroglycan could influence the anchorage of Dp116 and/or utrophin in normal and mdx Schwann cell membrane. We showed that metalloproteinase-9 was more activated in mdx nerve than in wild-type ones. This activation leads to an accumulation of the 30 kDa beta-dystroglycan isoform and has an impact on the anchorage of Dp116 and utrophin isoforms in mdx Schwann cells membrane. Our results showed that Dp116 had greater affinity to the full length form of beta-dystroglycan than the 30 kDa form. Moreover, we showed for the first time that the short isoform of utrophin (Up71) was over-expressed in mdx Schwann cells compared with wild-type. In addition, this utrophin isoform (Up71) seems to have greater affinity to the 30 kDa beta-dystroglycan which could explain the increased stabilization of this 30 kDa form at the membrane compartment. Our results highlight the potential participation of the short utrophin isoform and the cleaved form of beta-dystroglycan in mdx Schwann cell membrane architecture. We proposed that these two proteins could be implicated in Schwann cell proliferation in response to a microenvironment stress such as mediated by accumulating macrophages in mdx mouse muscle inflammation sites.
authors.affiliation: Université Montpellier 1, UFR de Médecine, Laboratoire de Physiologie des Interactions, EA 701, Institut de Biologie, 4 Boulevard Henri IV, 34000 Montpellier, France; Institut Supérieur de Biotechnologie and UR. 08/39 Faculté de Médecine, Monastir, Tunisia.
authors.forename: K
authors.initials: K
authors.lastname: Hnia
authors.affiliation: Université Montpellier 1, UFR de Médecine, Laboratoire de Physiologie des Interactions, EA 701, Institut de Biologie, 4 Boulevard Henri IV, 34000 Montpellier, France.
authors.forename: G
authors.initials: G
authors.lastname: Hugon
authors.affiliation: Institut Supérieur de Biotechnologie and UR. 08/39 Faculté de Médecine, Monastir, Tunisia.
authors.forename: A
authors.initials: A
authors.lastname: Masmoudi
authors.affiliation: Université Montpellier 1, UFR de Médecine, Laboratoire de Physiologie des Interactions, EA 701, Institut de Biologie, 4 Boulevard Henri IV, 34000 Montpellier, France.
authors.forename: J
authors.initials: J
authors.lastname: Mercier
authors.affiliation: Université Montpellier 1, UFR de Médecine, Laboratoire de Physiologie des Interactions, EA 701, Institut de Biologie, 4 Boulevard Henri IV, 34000 Montpellier, France.
authors.forename: F
authors.initials: F
authors.lastname: Rivier
authors.affiliation: Université Montpellier 1, UFR de Médecine, Laboratoire de Physiologie des Interactions, EA 701, Institut de Biologie, 4 Boulevard Henri IV, 34000 Montpellier, France. Electronic address: dominique.mornet@univ-montp1.fr.
authors.forename: D
authors.initials: D
authors.lastname: Mornet
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D049030:Dystroglycans / Q000378:metabolism*; D016189:Dystrophin / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D047468:Immunoprecipitation / Q000379:methods; D020780:Matrix Metalloproteinase 9 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx / Q000378:metabolism*; D008954:Models, Biological; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D009418:S100 Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology* / Q000187:drug effects; D012584:Sciatic Nerve / Q000166:cytology; D018709:Statistics, Nonparametric; D049411:Utrophin / Q000378:metabolism*
chemical_list: D016189:Dystrophin; D009418:S100 Proteins; D049411:Utrophin; D049030:Dystroglycans; D020780:Matrix Metalloproteinase 9