Human neural cell adhesion molecule L1 and rat homologue NILE are ligands for integrin αvβ3

Anthony M.P. Montgomery, Jurgen C. Becker, Chi Hung Siu, Vance P. Lemmon, David A. Cheresh, James D. Pancook, Xiaoning Zhao, Ralph A. Reisfeld

Research output: Contribution to journalArticlepeer-review

200 Scopus citations

Abstract

Integrin αvβ3 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, αvβ3 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 αv-integrin subunit and could be significantly inhibited by an antibody to the αvβ3 heterodimer. M21 cells also displayed some αvβ3-dependent adhesion and spreading on immunopurified human L1. Ligation between this ligand and αvβ3 was also observed to promote significant haptotactic cell migration. To map the site of αvβ3 ligation we used recombinant L1 fragments comprising the entire extracellular domain of human L1. Significant αvβ3-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 αvβ3-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, αvβ3 may recognize L1 in a cell-cell or cell-substrate interaction.

Original languageEnglish (US)
Pages (from-to)475-485
Number of pages11
JournalJournal of Cell Biology
Volume132
Issue number3
DOIs
StatePublished - Feb 1996
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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