Medizinische Universität Graz - Research portal
Selected Publication:
Montgomery, AMP; Becker, JC; Siu, CH; Lemmon, VP; Cheresh, DA; Pancook, JD; Zhao, XN; Reisfeld, RA.
Human neural cell adhesion molecule L1 and rat homologue NILE are ligands for integrin alpha v beta 3.
J Cell Biol. 1996; 132(3):475-485
Doi: 10.1083/jcb.132.3.475
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- Co-authors Med Uni Graz
- Becker Jürgen Christian
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Amino Acid Sequence -
- Animals -
- Antibodies -
- Antigens, Surface - metabolism
- Base Sequence -
- Binding Sites -
- Cell Adhesion -
- Cell Line -
- Cell Movement -
- DNA Primers -
- Humans -
- Kinetics -
- Leukocyte L1 Antigen Complex -
- Ligands -
- Melanoma -
- Molecular Sequence Data -
- Mutagenesis, Site-Directed -
- Neural Cell Adhesion Molecules - biosynthesis Neural Cell Adhesion Molecules - isolation and purification Neural Cell Adhesion Molecules - metabolism
- Oligopeptides -
- Polymerase Chain Reaction -
- Rats -
- Receptors, Vitronectin - metabolism
- Recombinant Fusion Proteins - biosynthesis Recombinant Fusion Proteins - isolation and purification Recombinant Fusion Proteins - metabolism
- Tumor Cells, Cultured -