Integrating Activities of Laminins That Drive Basement Membrane Assembly and Function

Curr Top Membr. 2015;76:1-30. doi: 10.1016/bs.ctm.2015.05.001. Epub 2015 Jun 25.

Abstract

Studies on extracellular matrix proteins, cells, and genetically modified animals have converged to reveal mechanisms of basement membrane self-assembly as mediated by γ1 subunit-containing laminins, the focus of this chapter. The basic model is as follows: A member of the laminin family adheres to a competent cell surface and typically polymerizes followed by laminin binding to the extracellular adaptor proteins nidogen, perlecan, and agrin. Assembly is completed by the linking of nidogen and heparan sulfates to type IV collagen, allowing it to form a second stabilizing network polymer. The assembled matrix provides structural support, anchoring the extracellular matrix to the cytoskeleton, and acts as a signaling platform. Heterogeneity of function is created in part by the isoforms of laminin that vary in their ability to polymerize and to interact with integrins, dystroglycan, and other receptors. Mutations in laminin subunits, affecting expression or LN domain-specific functions, are a cause of human diseases that include those of muscle, nerve, brain, and kidney.

Keywords: Agrin; Basement membrane; Collagen; Dystroglycan; Integrin; Muscular dystrophy; Myelination; Nidogen; Perlecan; Pierson syndrome.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Basement Membrane / metabolism*
  • Cell Adhesion
  • Collagen Type IV / metabolism
  • Cytoskeleton / metabolism
  • Humans
  • Laminin / chemistry
  • Laminin / deficiency
  • Laminin / metabolism*
  • Protein Multimerization

Substances

  • Collagen Type IV
  • Laminin