DOI: 10.1083/jcb.132.3.475. Human neural cell adhesion molecule L1 and rat homologue NILE are ligands for integrin alpha v beta 3.

Human neural cell adhesion molecule L1 and rat homologue NILE are ligands for integrin alpha v beta 3.

10.1083/jcb.132.3.475

Crossref journal-article

Rockefeller University Press

The Journal of cell biology (291)

Abstract

Integrin alpha v beta 3 is distinct in its capacity to recognize the sequence Arg-Gly-Asp (RGD) in many extra-cellular matrix (ECM) components. Here, we demonstrate that in addition to the recognition of ECM components, alpha v beta 3 can interact with the neural cell adhesion molecule L1-CAM; a member of the immunoglobulin superfamily (IgSF). M21 melanoma cells displayed significant Ca(++)-dependent adhesion and spreading on immunopurified rat L1 (NILE). This adhesion was found to be dependent on the expression of the alpha v-integrin subunit and could be significantly inhibited by an antibody to the alpha v beta 3 heterodimer. M21 cells also displayed some alpha v beta 3-dependent adhesion and spreading on immunopurified human L1. Ligation between this ligand and alpha v beta 3 was also observed to promote significant haptotactic cell migration. To map the site of alpha v beta 3 ligation we used recombinant L1 fragments comprising the entire extracellular domain of human L1. Significant alpha v beta 3-dependent adhesion and spreading was evident on a L1 fragment containing Ig-like domains 4, 5, and 6. Importantly, mutation of an RGD sequence present in the sixth Ig-like domain of L1 abrogated M21 cell adhesion. We conclude that alpha v beta 3-dependent recognition of human L1 is dependent on ligation of this RGD site. Despite high levels of L1 expression the M21 melanoma cells did not display significant adhesion via a homophilic L1-L1 interaction. These data suggest that M21 melanoma cells recognize and adhere to L1 through a mechanism that is primarily heterophilic and integrin dependent. Finally, we present evidence that melanoma cells can shed and deposit L1 in occluding ECM. In this regard, alpha v beta 3 may recognize L1 in a cell-cell or cell-substrate interaction.

Bibliography

Montgomery, A. M., Becker, J. C., Siu, C. H., Lemmon, V. P., Cheresh, D. A., Pancook, J. D., Zhao, X., & Reisfeld, R. A. (1996). Human neural cell adhesion molecule L1 and rat homologue NILE are ligands for integrin alpha v beta 3. The Journal of Cell Biology, 132(3), 475â485.

Authors 8

A M Montgomery (first)
J C Becker (additional)
C H Siu (additional)
V P Lemmon (additional)
D A Cheresh (additional)
J D Pancook (additional)
X Zhao (additional)
R A Reisfeld (additional)

References 0 Referenced 189

None

Dates

Type	When
Created	21 years, 3 months ago (May 14, 2004, 9:23 p.m.)
Deposited	2 years, 1 month ago (July 22, 2023, 2:14 a.m.)
Indexed	2 months ago (July 6, 2025, 1:44 p.m.)
Issued	29 years, 7 months ago (Feb. 1, 1996)
Published	29 years, 7 months ago (Feb. 1, 1996)
Published Online	29 years, 7 months ago (Feb. 1, 1996)
Published Print	29 years, 7 months ago (Feb. 1, 1996)

Funders 0

None

BibTeX

@article{Montgomery_1996, title={Human neural cell adhesion molecule L1 and rat homologue NILE are ligands for integrin alpha v beta 3.}, volume={132}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.132.3.475}, DOI={10.1083/jcb.132.3.475}, number={3}, journal={The Journal of cell biology}, publisher={Rockefeller University Press}, author={Montgomery, A M and Becker, J C and Siu, C H and Lemmon, V P and Cheresh, D A and Pancook, J D and Zhao, X and Reisfeld, R A}, year={1996}, month=feb, pages={475–485} }

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