Heparin modulation of laminin polymerization

Yurchenco, Peter D.; Cheng, Yi-Shan; Schittny, Johannes C. (1990). Heparin modulation of laminin polymerization. Journal of biological chemistry, 265(7), pp. 3981-3991. American Society for Biochemistry and Molecular Biology

Full text not available from this repository. (Request a copy)

Previously, it has been shown that laminin will self-assemble by a two-step calcium-dependent process using end-domain interactions (Yurchenco, P. D., Tsi-library, E. C., Charonis, A. S., and Furthmayr, H. (1985) J. Biol. Chem. 260, 7636-7644). We now find that heparin, at low concentrations, modifies this polymerization by driving the equilibrium further toward aggregation, by producing a denser polymer, and by inducing aggregation in the absence of calcium. This effect on self-assembly is specific in that it is observed with heparin but not with several heparan sulfates or other glycosaminoglycans: it correlates with affinity and depends on the degree of polysaccharide sulfation. Heparin binds to laminin in a calcium-dependent manner with a single class of interaction (KD = 118 +/- 18 nM) and with a binding capacity of one heparin for two laminins. We find the long arm globule (E3) is the only laminin domain which exhibits substantial heparin binding: heparin binds E3 with an affinity (KD = 94 +/- 12 nM) and calcium dependence similar to that for intact laminin. These data strongly suggest that heparin modifies laminin assembly by binding to pairs of long arm globular domains. As a result the polymer may be stabilized at domain E3 and laminin interdomain interactions induced or modified. We further postulate that heparins may act in vivo as specific regulators of the structure and functions of basement membranes by both altering the laminin matrix and by displacing weakly binding heparan sulfates.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Functional Anatomy

UniBE Contributor:

Schittny, Johannes

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

0021-9258

Publisher:

American Society for Biochemistry and Molecular Biology

Language:

English

Submitter:

Johannes Schittny

Date Deposited:

18 Aug 2014 12:17

Last Modified:

18 Aug 2014 12:17

PubMed ID:

2303489

URI:

https://boris.unibe.ch/id/eprint/50172

Actions (login required)

Edit item Edit item
Provide Feedback