Functional Modules

    Immunoglobulin superfamily (Ig) CAMs[Edit]

    Members of this family include vascular and neural cell adhesions molecules (VCAM and NCAM), intercellular adhesion molecules (ICAM) and the nectins and nectin-like (Necl) proteins. Nectins in particular are involved in the formation of cadherin-based cell-cell junctions [1], mediating initial cell-cell contacts via nectin-nectin or nectin-Necl binding and establishing links to the actin cytoskeleton via nectin-afadin binding [2]. Of the four major groups of CAMs, IgCAMs are the only group that function independently of calcium. 

    The Ig superfamily is a large group of cell surface molecules that includes members such as:
    • vascular cell adhesion molecules (VCAM)
    • neural cell adhesion molecules (NCAM)
    • intercellular adhesion molecules (ICAM)
    • nectin and nectin-like (Necl) family

    Figure 1. Schematic diagram of immunoglobulin superfamily members that are found in neurons: The extracytoplasmic portion of all Ig superfamily members is composed of a variable number of Ig domains (~3.7 nm per Ig domain) that together yield a final length of approximately 17-19 nm for both NCAM [3] and ICAM-1 [4]; certain Ig family members also contain a variable number of fibronectin III repeat domains. The transmembrane domain (TM) located at the extreme carboxy-terminus leaves a relatively small portion on the intracellular side for associating with other proteins. ICAM-1 is similar to ICAM-5 (not shown) but contains five Ig domains. Nectin and Necls share a similar structure, with three extracytoplasmic Ig-like domains (reviewed in [5])
    Members of the Ig superfamily resemble each other in their three-dimensional structure as well as their amino acid sequence (reviewed in [    6]). ICAMs and NCAMs form heterophilic and homophilic interactions (respectively) with adhesion molecules on other cells through a rigid extracytoplasmic rod domain that contains at least one flexible hinge domain [7, 8]. Although nectins and Necls form both heterophilic and homophilic interactions (reviewed in[1]), their homophilic interactions tend to be stronger [9].

    ICAM family

    Most ICAMs are expressed mainly by immune cells and endothelial cells, however brain-specific forms also exist (e.g. ICAM-5 aka TLCN) [10, 11]. All ICAMs appear to share lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18, αLβ2 integrin) as their counter receptor [12, 13, 14]. LFA-1 integrin is found on the surface of leukocytes where it modulates adhesion-dependent events that are essential for immune system activities. In the brain, LFA-1 expression appears to be restricted to resident macrophages (microglia) and its expression is tied to microglia activation [15]. ICAM-1 and LFA-1 binding is magnesium-dependent [12, 16] and the sites for LFA-1 binding lie in the first two amino-terminal Ig domains of ICAM-1; the residues involved in binding to LFA-1 are conserved in other ICAMs [7].

    Nectin and Necl family

    Nectins and nectin-like molecules (Necls) are expressed in a number of cell types where they have been shown to be important for cell-cell adhesion and the formation of stable junctions (e.g adherens junctions). Nectins and Necls also play a role in various cellular activities including cell polarization, migration, growth and cell fate (reviewed in [1, 17]). Nectin and Necls interact with and share a number of binding partners through their cytoplasmic domain, however, only nectins bind to afadin, an F-actin binding protein.

    References

    1. Takai Y., Nakanishi H. Nectin and afadin: novel organizers of intercellular junctions. J. Cell. Sci. 2003; 116(Pt 1). [PMID: 12456712]
    2. Kurita S., Ogita H., Takai Y. Cooperative role of nectin-nectin and nectin-afadin interactions in formation of nectin-based cell-cell adhesion. J. Biol. Chem. 2011; 286(42). [PMID: 21880730]
    3. Smith RJ., Bryant RG. Metal substitutions incarbonic anhydrase: a halide ion probe study. Biochem. Biophys. Res. Commun. 1975; 66(4). [PMID: 3]
    4. Bose KS., Sarma RH. Delineation of the intimate details of the backbone conformation of pyridine nucleotide coenzymes in aqueous solution. Biochem. Biophys. Res. Commun. 1975; 66(4). [PMID: 2]
    5. Wiesmann UN., DiDonato S., Herschkowitz NN. Effect of chloroquine on cultured fibroblasts: release of lysosomal hydrolases and inhibition of their uptake. Biochem. Biophys. Res. Commun. 1975; 66(4). [PMID: 4]
    6. Takada Y., Ye X., Simon S. The integrins. Genome Biol. 2007; 8(5). [PMID: 17543136]
    7. Staunton DE., Dustin ML., Erickson HP., Springer TA. The arrangement of the immunoglobulin-like domains of ICAM-1 and the binding sites for LFA-1 and rhinovirus. Cell 1990; 61(2). [PMID: 1970514]
    8. Becker JW., Erickson HP., Hoffman S., Cunningham BA., Edelman GM. Topology of cell adhesion molecules. Proc. Natl. Acad. Sci. U.S.A. 1989; 86(3). [PMID: 2915974]
    9. Satoh-Horikawa K., Nakanishi H., Takahashi K., Miyahara M., Nishimura M., Tachibana K., Mizoguchi A., Takai Y. Nectin-3, a new member of immunoglobulin-like cell adhesion molecules that shows homophilic and heterophilic cell-cell adhesion activities. J. Biol. Chem. 2000; 275(14). [PMID: 10744716]
    10. Mori K., Fujita SC., Watanabe Y., Obata K., Hayaishi O. Telencephalon-specific antigen identified by monoclonal antibody. Proc. Natl. Acad. Sci. U.S.A. 1987; 84(11). [PMID: 3295872]
    11. Yoshihara Y., Oka S., Nemoto Y., Watanabe Y., Nagata S., Kagamiyama H., Mori K. An ICAM-related neuronal glycoprotein, telencephalin, with brain segment-specific expression. Neuron 1994; 12(3). [PMID: 7794412]
    12. Marlin SD., Springer TA. Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen 1 (LFA-1). Cell 1987; 51(5). [PMID: 3315233]
    13. Staunton DE., Dustin ML., Springer TA. Functional cloning of ICAM-2, a cell adhesion ligand for LFA-1 homologous to ICAM-1. Nature 1989; 339(6219). [PMID: 2497351]
    14. Mizuno T., Yoshihara Y., Kagamiyama H., Ohsawa K., Imai Y., Kohsaka S., Mori K. Neuronal adhesion molecule telencephalin induces rapid cell spreading of microglia. Brain Res. 1999; 849(1-2). [PMID: 10592287]
    15. Moneta ME., Gehrmann J., Töpper R., Banati RB., Kreutzberg GW. Cell adhesion molecule expression in the regenerating rat facial nucleus. J. Neuroimmunol. 1993; 45(1-2). [PMID: 8101190]
    16. Dustin ML., Springer TA. T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1. Nature 1989; 341(6243). [PMID: 2477710]
    17. Takai Y., Miyoshi J., Ikeda W., Ogita H. Nectins and nectin-like molecules: roles in contact inhibition of cell movement and proliferation. Nat. Rev. Mol. Cell Biol. 2008; 9(8). [PMID: 18648374]
    Updated on: Wed, 26 Feb 2014 10:55:36 GMT
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