The laminin alpha2-chain short arm mediates cell adhesion through both the alpha1beta1 and alpha2beta1 integrins.
Laminin-2, a heterotrimer composed of alpha2, beta1, and gamma1 subunits, is the primary laminin isoform found in muscle and peripheral nerve and is essential for the development and stability of basement membranes in these tissues. Expression of a domain VI-truncated laminin alpha2-chain results in muscle degeneration and peripheral nerve dysmyelination in the dy2J dystrophic mouse. We have expressed amino-terminal domains VI through IVb of the laminin alpha2-chain, as well as its laminin-1 alpha1-chain counterpart, to identify candidate cell-interactive functions of this critical region. Using integrin-specific antibodies, recognition sites for the alpha1beta1 and alpha2beta1 integrins were identified in the short arms of both laminin alpha1- and alpha2-chain isoforms. Comparisons with a beta-alpha chimeric short arm protein possessing beta1-chain domain VI further localized these activities to alpha-chain domain VI. In addition, we found that the laminin alpha2-chain short arm supported neurite outgrowth independent of other laminin-2 subunits. A heparin/heparan sulfate binding activity was also localized to this region of the laminin alpha2 subunit. These data provide the first evidence that domain VI of the laminin alpha2-chain mediates interactions with cell surface receptors and suggest that these integrin and heparin binding sites, alone or in concert, may play an important role in muscle and peripheral nerve function.
Colognato
H
H
Department of Pathology, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
MacCarrick
M
M
O'Rear
J J
JJ
Yurchenco
P D
PD
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002448:Cell Adhesion / Q000502:physiology*; D005354:Fibrosarcoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D039222:Integrin alpha1beta1; D016023:Integrins / Q000502:physiology*; D007797:Laminin / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D016501:Neurites; D038981:Receptors, Collagen; D014407:Tumor Cells, Cultured
D039222:Integrin alpha1beta1; D016023:Integrins; D007797:Laminin; D038981:Receptors, Collagen; C102645:laminin alpha 2