Neural cell adhesion molecule (N-CAM) homophilic binding mediated by the two N-terminal Ig domains is influenced by intramolecular domain-domain interactions.

The Journal of Biological Chemistry
A R AtkinsB A Cunningham

Abstract

The mechanism by which the neural cell adhesion molecule, N-CAM, mediates homophilic interactions between cells has been variously attributed to an isologous interaction of the third immunoglobulin (Ig) domain, to reciprocal binding of the two N-terminal Ig domains, or to reciprocal interactions of all five Ig domains. Here, we have used a panel of recombinant proteins in a bead binding assay, as well as transfected and primary cells, to clarify the molecular mechanism of N-CAM homophilic binding. The entire extracellular region of N-CAM mediated bead aggregation in a concentration- and temperature-dependent manner. Interactions of the N-terminal Ig domains, Ig1 and Ig2, were essential for bead binding, based on deletion and mutation experiments and on antibody inhibition studies. These findings were largely in accord with aggregation experiments using transfected L cells or primary chick brain cells. Additionally, maximal binding was dependent on the integrity of the intramolecular domain-domain interactions throughout the extracellular region. We propose that these interactions maintain the relative orientation of each domain in an optimal configuration for binding. Our results suggest that the role of Ig3 in homophilic bindi...Continue Reading

References

Jan 1, 1991·Annual Review of Biochemistry·G M Edelman, K L Crossin
Jun 1, 1987·The Journal of Cell Biology·A K Hall, U Rutishauser
Feb 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·J W BeckerG M Edelman
Jan 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·R BrackenburyG M Edelman
May 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·B A CunninghamG M Edelman
Aug 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·R BertolottiG M Edelman
Jan 1, 1994·International Journal of Cancer. Supplement = Journal International Du Cancer. Supplement·R Gerardy-Schahn, M Eckhardt
Apr 30, 1996·Proceedings of the National Academy of Sciences of the United States of America·T S RanheimB A Cunningham
Oct 28, 1998·Cell Adhesion and Communication·A PierresP Bongrand
May 10, 2000·Nature Structural Biology·C KasperI K Larsen
Jun 8, 2000·Developmental Dynamics : an Official Publication of the American Association of Anatomists·K L Crossin, L A Krushel
Jun 16, 2001·Molecular Biology of the Cell·G SchürmannH P Erickson
Jul 13, 2001·The Journal of Cell Biology·S Chappuis-FlamentB M Gumbiner
May 29, 2003·Biophysical Journal·B ZhuD Leckband
Feb 27, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Luis Polo-ParadaLynn T Landmesser
May 1, 2004·Proceedings of the National Academy of Sciences of the United States of America·C P JohnsonD Leckband

❮ Previous
Next ❯

Citations

Jun 20, 2012·Nature Chemical Biology·Peter Tompa
Sep 2, 2008·Neurochemical Research·Vladislav SorokaFlemming M Poulsen
Oct 14, 2008·Gene Expression Patterns : GEP·Shunsaku HommaHiroyuki Yaginuma
Feb 12, 2008·Journal of Molecular Biology·Federico CarafoliErhard Hohenester
Apr 23, 2009·Biophysical Journal·Venkat MaruthamuthuDeborah Leckband
Sep 19, 2006·Biophysical Journal·Fabien Cailliez, Richard Lavery
Feb 27, 2007·The Journal of Biological Chemistry·Dan SjöstrandCarlos F Ibáñez

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Cell Adhesion Molecules in the Brain

Cell adhesion molecules found on cell surface help cells bind with other cells or the extracellular matrix to maintain structure and function. Here is the latest research on their role in the brain.