The Laminin α2-Chain Short Arm Mediates Cell Adhesion through Both the α1β1 and α2β1 Integrins*
Abstract
Laminin-2, a heterotrimer composed of α2, β1, and γ1 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 α2-chain results in muscle degeneration and peripheral nerve dysmyelination in the dy 2Jdystrophic mouse. We have expressed amino-terminal domains VI through IVb of the laminin α2-chain, as well as its laminin-1 α1-chain counterpart, to identify candidate cell-interactive functions of this critical region. Using integrin-specific antibodies, recognition sites for the α1β1 and α2β1 integrins were identified in the short arms of both laminin α1- and α2-chain isoforms. Comparisons with a β-α chimeric short arm protein possessing β1-chain domain VI further localized these activities to α-chain domain VI. In addition, we found that the laminin α2-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 α2 subunit. These data provide the first evidence that domain VI of the laminin α2-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.
Footnotes
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↵* This project was supported by National Institutes of Health Grants R01-DK36425 and R01-DK48045.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ To whom correspondence should be addressed: Dept. of Pathology, Robert W. Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854. Tel.: 908-235-4674; Fax: 908-235-4825; E-mail: yurchenc{at}rwja.umdnj.edu.
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↵2 H. Colognato and P. D. Yurchenco, unpublished observations.
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↵3 Cheng, Y.-S., Champliaud, M.-F., Burgesson, R. E., Marinkovich, M. P., and Yurchenco, P. D. (1997) J. Biol. Chem. 272, in press.
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↵1 The abbreviations used are: EHS, Engelbreth-Holm-Swarm; PMSF, phenylmethylsulfonyl fluoride; HPLC, high pressure liquid chromatography.
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↵4 H. Colognato and P. D. Yurchenco, unpublished observations.
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- Received April 11, 1997.
- Revision received April 28, 1997.
