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Purification of the Dendritic Filopodia-rich Fraction
Published on: May 2, 2019
The neuronal glycoprotein telencephalin is a cellular ligand for the CD11a/CD18 leukocyte integrin
L Tian1, Y Yoshihara, T Mizuno
1Department of Biosciences, Division of Biochemistry, University of Helsinki, Finland.
Insights
Telencephalin (TLN), a novel central nervous system molecule, interacts with leukocyte integrins CD11a/CD18. This interaction, mediated by TLN's N-terminal domains, suggests a role in neuro-immune cell adhesion.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Leukocyte functions rely on beta2 integrins (CD11/CD18) binding to intercellular adhesion molecules (ICAMs).
- Telencephalin (TLN), an Ig superfamily member, is expressed in the central nervous system and shares homology with known ICAM ligands.
Purpose of the Study:
- To investigate the interaction between Telencephalin (TLN) and leukocyte integrins CD11a/CD18.
- To identify the specific domains of TLN involved in this interaction.
Main Methods:
- Adhesion assays using peripheral blood T cells, Jurkat T cells, and B lymphoblastoid cells with recombinant human TLN.
- Inhibition studies using antibodies against CD11a/CD18.
- Binding assays with TLN-transfected L cells and purified CD11a/CD18.
- Testing binding of truncated TLN proteins (TLN(1-5) and TLN(1-9)) to CD11a/CD18.
Main Results:
- Peripheral blood T cells, Jurkat T cells, and B lymphoblastoid cells demonstrated adhesion to recombinant TLN.
- This adhesion was confirmed to be mediated by CD11a/CD18 and was inhibited by anti-CD11a/CD18 antibodies.
- TLN-transfected cells also bound to purified CD11a/CD18, and TLN domains 1-5 were sufficient for binding.
Conclusions:
- Telencephalin (TLN) is a novel neuronal cell adhesion molecule that interacts with CD11a/CD18.
- The CD11a/CD18 recognition site on TLN is located within its N-terminal five Ig-like domains.
- This interaction may play a significant role in integrin-mediated cell-cell interactions within the central nervous system.
Abstract:
Many leukocyte functions depend on interactions between the leukocyte-specific beta2 integrins CD11/CD18 and their ligands, the intercellular adhesion molecules (ICAMs). Telencephalin (TLN) is a novel member of the Ig superfamily expressed in the central nervous system. The NH2-terminal five Ig-like domains of TLN show the highest homology with the Ig domains of ICAM-1, ICAM-2, ICAM-3, and LW (ICAM-4), the known cellular ligands for CD11a/CD18. Here, we demonstrate that TLN interacts with CD11a/CD18. Peripheral blood T cells, Jurkat T cells, and B lymphoblastoid cells bound to immunopurified recombinant human TLN proteins. This adhesion was through CD11a/CD18 and was significantly inhibited by an Ab to CD11a/CD18. Reciprocally, TLN-transfected L cells also bound to purified CD11a/CD18. Recombinant TLN proteins comprising either the first five Ig domains (TLN(1-5)) or the entire extracellular portion (TLN(1-9)) showed binding to CD11a/CD18. We conclude that TLN is a novel neuronal cell adhesion molecule that may be important in integrin-mediated cell-cell interactions in the central nervous system, and that the CD11a/CD18-dependent recognition site of human TLN is located within the NH2-terminal five domains of this molecule.
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