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J. Biol. Chem., Vol. 280, Issue 1, 137-145, January 7, 2005
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From the
Department of Chemistry and the ¶Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, the ||Department of Chemical and Biomolecular Engineering, University of Illinois, Urbana, Illinois, 61801, and the Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021
Molecular force measurements quantified the impact of polysialylation on the adhesive properties both of membrane-bound neural cell adhesion molecule (NCAM) and of other proteins on the same membrane. These results show quantitatively that NCAM polysialylation increases the range and magnitude of intermembrane repulsion. The repulsion is sufficient to overwhelm both homophilic NCAM and cadherin attraction at physiological ionic strength, and it abrogates the protein-mediated intermembrane adhesion. The steric repulsion is ionic strength dependent and decreases substantially at high monovalent salt concentrations with a concomitant increase in the intermembrane attraction. The magnitude of the repulsion also depends on the amount of polysialic acid (PSA) on the membranes, and the PSA-dependent attenuation of cadherin adhesion increases with increasing PSA-NCAM:cadherin ratios. These findings agree qualitatively with independent reports based on cell adhesion studies and reveal the likely molecular mechanism by which NCAM polysialylation regulates cell adhesion and intermembrane space.
Received for publication, September 7, 2004 , and in revised form, October 15, 2004.
* This work was supported by National Institutes of Health Grant 1RO1 GM33986. The Laboratory for Fluorescence Dynamics is a National Institute of Health National Resource and is also partially supported by the University of Illinois. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
** To whom correspondence should be addressed. Tel.: 217-244-0793; Fax: 217-333-5052; E-mail: leckband{at}uiuc.edu.
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