Advertisement

Discovery of Basement Membrane Components

  • M. Peter Marinkovich
    Correspondence
    Department of Dermatology, Stanford University School of Medicine; 269 Campus Dr. no. 2145, Stanford, California 94305, USA
    Affiliations
    Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA
    Search for articles by this author
      The dermal-epidemal basement membrane can arguably be said to be the most well studied of all basement membranes, and is a structure that plays an important role in cutaneous biology. While the discovery of genes coding for basement membrane components has provided exciting advances in our understanding of the basement membrane zone, it is easy to forget that initial molecular discovery of the major basement membrane zone proteins took place largely at the protein level. Indeed, in many instances the biochemical characterization of basement membrane zone (BMZ) proteins created the foundation for the subsequent molecular biologic advances.
      The entire field of basement membrane biochemistry as we know it today was pioneered during a highly productive period of work by a group at the Max Planck Institute in Germany during the late 1970s and 1980s, which included Drs Rupert Timpl and George Martin. The activity of this group catapulted the field forward, and Dr Timpl continued this work until his untimely death in October 2003. During this period, a great many of the current leading figures in BMZ biology received their training in this group, and Timpl, Martin and others isolated and characterized the major BMZ components from the Engelbreth–Holm–Swarm tumor. The isolation and characterization of laminins, type IV collagen, nidogen (also known as entactin) and a heparan sulfate proteoglycan, ultimately named perlecan, provided a foundation for future studies at both the protein and molecular level (
      • Timpl R.
      • Martin G.
      • Bruckner P.
      • Wick G.
      • Wiedemann H.
      Nature of the collagenous protein in a tumor basement membrane.
      ,
      • Timpl R.
      • Rohde H.
      • Robey P.
      • Rennard S.
      • Foidart J.
      • Martin G.
      Laminin-a glycoprotein from basement membranes.
      ,
      • Martin G.
      • Timpl R.
      Laminin and other basement membrane components.
      ).
      Subsequent to the discoveries of the major ubiquitous BMZ components from Engelbreth-Holm-Swarm tumors, a number of important associated and specialized BMZ components were discovered. Type VII collagen was discovered in the early 1980s, which coincided with our appreciation of this molecule's roles in acquired and inherited skin disease (
      • Woodley D.T.
      • Burgeson R.E.
      • Lunstrum G.
      • Bruckner-Tuderman L.
      • Reese M.J.
      • Briggaman R.A.
      Epidermolysis bullosa acquisita antigen is the globular carboxyl terminus of type VII procollagen.
      ,
      • Burgeson R.E.
      • Lundstrum G.P.
      • Rokosova B.
      The structure and function of type VII collagen.
      ). At the same time, the BMZ-associated molecule fibrillin, which was proven to show altered expression in Marfan's syndrome (
      • Sakai L.Y.
      • Keene D.R.
      • Engvall E.
      Fibrillin, a new 350-kDa glycoprotein, is a component of extracellular microfibrils.
      ), was also discovered.
      During the late 1980s and early 1990s, it became clear that multiple isoforms of laminins existed (
      • Ehrig K.
      • Leivo I.
      • Argraves W.S.
      • Ruoslahti E.
      • Engvall E.
      Merosin, a tissue-specific basement membrane protein, is a laminin-like protein.
      ). Some of these isoforms had important roles in the skin, most especially laminin-5, which was independently discovered by three separate groups (
      • Verrando P.
      • Pisani A.
      • Ortonne J.P.
      The new basement membrane antigen recognized by monoclonal antibody GB3 is a large size weight glycoprotein: modulation of its expression by retinoic acid.
      ,
      • Carter W.G.
      • Ryan M.C.
      • Gahr P.J.
      Epiligrin, a new cell adhesion ligand for integrin-3-1 in epithelial basement membranes.
      ,
      • Rousselle P.
      • Lunstrum G.P.
      • Keene D.R.
      • Burgeson R.E.
      Kalinin: an epithelium-specific basement membrane adhesion molecule that is a component of anchoring filaments.
      ), as well as laminin-6 (
      • Marinkovich M.P.
      • Lundstrum G.P.
      • Keene D.R.
      • Burgeson R.E.
      The dermal-epidermal junction of human skin contains a novel laminin variant.
      ) and laminin-10/11 (
      • Miner J.
      • Lewis R.
      • Sanes J.
      Molecular cloning of a novel laminin chain, alpha 5, and widespread expression in adult mouse tissues.
      ). Shortly after this report, laminin 5 was found to be the target antigen for patients with a form of mucosal pemphigoid (
      • Domloge-Hultsch N.
      • Gammon W.R.
      • Briggaman R.A.
      • Gil S.G.
      • Carter W.G.
      • Yancey K.B.
      Epiligrin, the major human keratinocyte integrin ligand, is a target in both an acquired autoimmune and an inherited subepidermal blistering skin disease.
      ). Nomenclature has always been a favorite subject of laminin biologists, and recently a new terminology has been adopted, which lists the numbers of the α-, β- and γ-subunits in succession. Thus laminin-5, 6 and 10 are now known as laminin-332, 311, and 511 (
      • Aumailley M.
      • Bruckner-Tuderman L.
      • Carter W.G.
      • Deutzmann R.
      • Edgar D.
      • Ekblom P.
      • et al.
      A simplified laminin nomenclature.
      ).
      Finally, the topic of BMZ biochemistry cannot be complete without mentioning the discovery of the hemi-desmosome proteins. Discoveries of bullous pemphigold (BP) antigens (
      • Stanley J.
      • Hawley-Nelson P.
      • Yuspa S.
      • Shevach E.
      • Katz S.
      Characterization of bullous pemphigoid antigen: a unique basement membrane protein of stratified squamous epithelia.
      ,
      • Diaz L.A.
      • Ratrie H.
      • Saunders W.S.
      • Futamura S.
      • Squiquera H.L.
      • Anhalt G.J.
      • et al.
      Isolation of a human epidermal cDNA corresponding to the 180-kDa autoantigen recognized by bullous pemphigoid and herpes gestationis sera. Immunolocalization of this protein to the hemidesmosome.
      ), plectin (
      • Wiche G.
      • Herrmann H.
      • Leichtfried F.
      • Pytela R.
      Plectin: a high-molecular-weight cytoskeletal polypeptide component that copurifies with intermediate filaments of the vimentin type.
      ) and a6b4 integrin (
      • Sonnenberg A.
      • Modderman P.W.
      • Hogervorst F.
      Laminin receptor on platelets is the integrin VLA-6.
      ) in the 1980s and early 1990s all led to extensive subsequent investigations of the role of these molecules in a variety of human diseases, including cancer, inherited and autoimmune blistering diseases and wound healing. Notably, it has been the study of skin biology and skin cells that has propelled much of this research forward.

      REFERENCES

        • Aumailley M.
        • Bruckner-Tuderman L.
        • Carter W.G.
        • Deutzmann R.
        • Edgar D.
        • Ekblom P.
        • et al.
        A simplified laminin nomenclature.
        Matrix Biol. 2005; 24: 326-332
        • Burgeson R.E.
        • Lundstrum G.P.
        • Rokosova B.
        The structure and function of type VII collagen.
        Ann NY Acad Sci. 1990; 580: 32-43
        • Carter W.G.
        • Ryan M.C.
        • Gahr P.J.
        Epiligrin, a new cell adhesion ligand for integrin-3-1 in epithelial basement membranes.
        Cell. 1991; 65: 559-610
        • Diaz L.A.
        • Ratrie H.
        • Saunders W.S.
        • Futamura S.
        • Squiquera H.L.
        • Anhalt G.J.
        • et al.
        Isolation of a human epidermal cDNA corresponding to the 180-kDa autoantigen recognized by bullous pemphigoid and herpes gestationis sera. Immunolocalization of this protein to the hemidesmosome.
        J Clin Invest. 1990; 86: 1088-1094
        • Domloge-Hultsch N.
        • Gammon W.R.
        • Briggaman R.A.
        • Gil S.G.
        • Carter W.G.
        • Yancey K.B.
        Epiligrin, the major human keratinocyte integrin ligand, is a target in both an acquired autoimmune and an inherited subepidermal blistering skin disease.
        J Clin Invest. 1992; 90: 1628-1633
        • Ehrig K.
        • Leivo I.
        • Argraves W.S.
        • Ruoslahti E.
        • Engvall E.
        Merosin, a tissue-specific basement membrane protein, is a laminin-like protein.
        Proc Natl Acad Sci USA. 1990; 87: 3264-3268
        • Marinkovich M.P.
        • Lundstrum G.P.
        • Keene D.R.
        • Burgeson R.E.
        The dermal-epidermal junction of human skin contains a novel laminin variant.
        J Cell Biol. 1992; 119: 695-703
        • Martin G.
        • Timpl R.
        Laminin and other basement membrane components.
        Annu Rev Cell Biol. 1987; 3: 57-85
        • Miner J.
        • Lewis R.
        • Sanes J.
        Molecular cloning of a novel laminin chain, alpha 5, and widespread expression in adult mouse tissues.
        J Biol Chem. 1995; 270: 28523-28526
        • Rousselle P.
        • Lunstrum G.P.
        • Keene D.R.
        • Burgeson R.E.
        Kalinin: an epithelium-specific basement membrane adhesion molecule that is a component of anchoring filaments.
        J Cell Biol. 1991; 114: 567-576
        • Sakai L.Y.
        • Keene D.R.
        • Engvall E.
        Fibrillin, a new 350-kDa glycoprotein, is a component of extracellular microfibrils.
        J Cell Biol. 1986; 103: 2499-2509
        • Sonnenberg A.
        • Modderman P.W.
        • Hogervorst F.
        Laminin receptor on platelets is the integrin VLA-6.
        Nature. 1988; 336: 487-489
        • Stanley J.
        • Hawley-Nelson P.
        • Yuspa S.
        • Shevach E.
        • Katz S.
        Characterization of bullous pemphigoid antigen: a unique basement membrane protein of stratified squamous epithelia.
        Cell. 1981; 24: 897-903
        • Timpl R.
        • Martin G.
        • Bruckner P.
        • Wick G.
        • Wiedemann H.
        Nature of the collagenous protein in a tumor basement membrane.
        Eur J Biochem. 1978; 84: 43-52
        • Timpl R.
        • Rohde H.
        • Robey P.
        • Rennard S.
        • Foidart J.
        • Martin G.
        Laminin-a glycoprotein from basement membranes.
        J Biol Chem. 1979; 254: 9933-9937
        • Verrando P.
        • Pisani A.
        • Ortonne J.P.
        The new basement membrane antigen recognized by monoclonal antibody GB3 is a large size weight glycoprotein: modulation of its expression by retinoic acid.
        Biochim Biophys Acta. 1988; 942: 45-56
        • Wiche G.
        • Herrmann H.
        • Leichtfried F.
        • Pytela R.
        Plectin: a high-molecular-weight cytoskeletal polypeptide component that copurifies with intermediate filaments of the vimentin type.
        Cold Spring Harb Symp Quant Biol. 1982; 46: 475-482
        • Woodley D.T.
        • Burgeson R.E.
        • Lunstrum G.
        • Bruckner-Tuderman L.
        • Reese M.J.
        • Briggaman R.A.
        Epidermolysis bullosa acquisita antigen is the globular carboxyl terminus of type VII procollagen.
        J Clin Invest. 1988; 81: 683-687