Mapping of network-forming, heparin-binding, and alpha 1 beta 1 integrin-recognition sites within the alpha-chain short arm of laminin-1

J Biol Chem. 1995 Apr 21;270(16):9398-406. doi: 10.1074/jbc.270.16.9398.

Abstract

Cell-interactive and architecture-forming functions are associated with the short arms of basement membrane laminin-1. To map and characterize these functions, we expressed recombinant mouse laminin-1 alpha-chain extending from the N terminus through one third of domain IIIb. This dumbbell-shaped glycoprotein (r alpha 1(VI-IVb)'), secreted by mammalian cells, was found to possess three activities. 1) Laminin polymerization was quantitatively inhibited by recombinant protein, supporting an alpha-chain role for a three-short arm interaction model of laminin self-assembly. 2) r alpha 1(VI-IVb)' bound to heparin, and the activity was localized to a subfragment corresponding to domain VI by 125I-heparin blotting. 3) PC12 rat pheochromocytoma cells adhered to, and rapidly extended branching neurites on, r alpha 1(VI-IVb)', with adhesion inhibited by alpha 1 and beta 1 integrin chain-specific antibodies. The ability of anti-laminin antibody to block PC12 cell adhesion to laminin was selectively prevented by absorption with r alpha 1(VI-IVb)' or alpha-chain domain VI fragment. This active integrin-recognition site could furthermore be distinguished from a second cryptic alpha 1 beta 1-binding site exposed by heat treatment of fragment P1', a short arm fragment lacking globules. Thus, a polymer-forming, a heparin-binding, and the active alpha 1 beta 1 integrin-recognition site are all clustered at the end of the alpha-chain short arm, the latter two resident solely in domain VI.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Cells, Cultured
  • Heparin / metabolism*
  • Humans
  • Integrin alpha1beta1
  • Integrins / metabolism*
  • Laminin / chemistry*
  • Laminin / physiology*
  • Molecular Sequence Data
  • Neurites / physiology*
  • Rabbits
  • Recombinant Proteins / chemistry

Substances

  • Integrin alpha1beta1
  • Integrins
  • Laminin
  • Recombinant Proteins
  • Heparin