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.
Article|
February 01 1996
Human neural cell adhesion molecule L1 and rat homologue NILE are ligands for integrin alpha v beta 3.
A M Montgomery,
A M Montgomery
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
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J C Becker,
J C Becker
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
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C H Siu,
C H Siu
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
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V P Lemmon,
V P Lemmon
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
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D A Cheresh,
D A Cheresh
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
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J D Pancook,
J D Pancook
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
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X Zhao,
X Zhao
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
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R A Reisfeld
R A Reisfeld
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
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A M Montgomery
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
J C Becker
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
C H Siu
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
V P Lemmon
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
D A Cheresh
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
J D Pancook
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
X Zhao
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
R A Reisfeld
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
Online ISSN: 1540-8140
Print ISSN: 0021-9525
J Cell Biol (1996) 132 (3): 475–485.
Citation
A M Montgomery, J C Becker, C H Siu, V P Lemmon, D A Cheresh, J D Pancook, X Zhao, R A Reisfeld; Human neural cell adhesion molecule L1 and rat homologue NILE are ligands for integrin alpha v beta 3.. J Cell Biol 1 February 1996; 132 (3): 475–485. doi: https://doi.org/10.1083/jcb.132.3.475
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