RGD Reference Report - Human neural cell adhesion molecule L1 and rat homologue NILE are ligands for integrin alpha v beta 3. - Rat Genome Database

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

Authors: Montgomery, AM  Becker, JC  Siu, CH  Lemmon, VP  Cheresh, DA  Pancook, JD  Zhao, X  Reisfeld, RA 
Citation: Montgomery AM, etal., J Cell Biol. 1996 Feb;132(3):475-85.
RGD ID: 11570518
Pubmed: PMID:8636223   (View Abstract at PubMed)
PMCID: PMC2120722   (View Article at PubMed Central)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of cell-substrate adhesion  IDA 11570518 RGD 

Objects Annotated

Genes (Rattus norvegicus)
L1cam  (L1 cell adhesion molecule)


Additional Information