title: Dystroglycan in skin and cutaneous cells: beta-subunit is shed from the cell surface.
abstract: In skin, hemidesmosomal protein complexes attach the epidermis to the dermis and are critical for stable connection of the basal epithelial cell cytoskeleton with the basement membrane (BM). In muscle, a similar supramolecular aggregate, the dystrophin glycoprotein complex links the inside of muscle cells with the BM. A component of the muscle complex, dystroglycan (DG), also occurs in epithelia. In this study, we characterized the expression and biochemical properties of authentic and recombinant DG in human skin and cutaneous cells in vitro. We show that DG is present at the epidermal BM zone, and it is produced by both keratinocytes and fibroblasts in vitro. The biosynthetic precursor is efficiently processed to the alpha- and beta-DG subunits; and, in addition, a distinct extracellular segment of the transmembranous beta-subunit is shed from the cell surface by metalloproteinases. Shedding of the beta-subunit releases the alpha-subunit from the DG complex on the cell surface into the extracellular space. The shedding is enhanced by IL-1beta and phorbol esters, and inhibited by metalloproteinase inhibitors. Deficiency of perlecan, a major ligand of alpha-DG, enhanced shedding suggesting that lack of a binding partner destabilizes the epithelial DG complex and makes it accessible to proteolytic processing.
authors.affiliation: Institute for Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Herzog
authors.forename: Cristina
authors.initials: C
authors.lastname: Has
authors.forename: Claus-Werner
authors.initials: CW
authors.lastname: Franzke
authors.forename: Frank G
authors.initials: FG
authors.lastname: Echtermeyer
authors.forename: Ursula
authors.initials: U
authors.lastname: Schlötzer-Schrehardt
authors.forename: Stephan
authors.initials: S
authors.lastname: Kröger
authors.forename: Erika
authors.initials: E
authors.lastname: Gustafsson
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
authors.forename: Leena
authors.initials: L
authors.lastname: Bruckner-Tuderman
mesh_terms: D002460:Cell Line; D003470:Culture Media; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020405:Dermis / Q000166:cytology* / Q000378:metabolism; D049030:Dystroglycans; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D014162:Transfection
chemical_list: D003470:Culture Media; D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D049030:Dystroglycans