TGF-beta1 binding protein-like modules of fibrillin-1 and -2 mediate integrin-dependent cell adhesion

Connect Tissue Res. 1998;37(1-2):29-51. doi: 10.3109/03008209809028898.

Abstract

Human fibrillin, a major component of the extracellular matrix, exists as two highly homologous forms (fibrillin-1 and -2). Several modules of fibrillin are homologous to TGF-beta1 binding protein. Two of these modules, D25 (the 25th module of fibrillin-1 and -2 D segment) and D12 (the 12th module of fibrillin-2 D segment) contain the cell adhesion motif arginyl-glycyl-aspartyl (RGD). The ability of RGD to mediate adhesion to D25-1 and D12-2 was investigated using bacterially expressed fusion proteins. Human skin fibroblasts and murine L-cells were used in microassays of cell attachment and cell spreading on fibrillin fusion-protein substrata. Dose-dependent experiments and competitive inhibition by soluble RGD-containing peptides demonstrated that D25-1 and D12-2 mediate RGD-dependent cell adhesion. These results provide evidence for a cell adhesion function of fibrillin-2. Inhibition with anti-integrin antibodies showed that alpha(v) and beta3 integrins mediate adhesion to D25-1, while alpha3, alpha(v) and beta1 are involved in adhesion to D12-2. Binding of different receptors may elicit distinct cell signalling supporting the hypothesis that fibrillin-1 and fibrillin-2 have distinct roles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / physiology*
  • Cell Adhesion / drug effects
  • Collagen / pharmacology
  • Cytoskeleton / drug effects
  • Fibrillin-1
  • Fibrillin-2
  • Fibrillins
  • Fibronectins / pharmacology
  • Humans
  • Integrins / physiology*
  • Intracellular Signaling Peptides and Proteins*
  • L Cells
  • Latent TGF-beta Binding Proteins
  • Mice
  • Microfilament Proteins / physiology*
  • Molecular Sequence Data
  • Peptides / chemical synthesis
  • Peptides / metabolism
  • Protein Binding / drug effects
  • Sequence Homology, Amino Acid
  • Serum Albumin, Bovine / pharmacology

Substances

  • Carrier Proteins
  • FBN1 protein, human
  • FBN2 protein, human
  • Fbn1 protein, mouse
  • Fbn2 protein, mouse
  • Fibrillin-1
  • Fibrillin-2
  • Fibrillins
  • Fibronectins
  • Integrins
  • Intracellular Signaling Peptides and Proteins
  • Latent TGF-beta Binding Proteins
  • Microfilament Proteins
  • Peptides
  • Serum Albumin, Bovine
  • Collagen