Immunoglobulin superfamily receptors: cis-interactions, intracellular adapters and alternative splicing regulate adhesion.
The immunoglobulin domain is a module found in vertebrates and invertebrates. Its ability to form linear rods when deployed in series, combined with its propensity to bind specifically to other proteins has made it ideal for building cell surface receptors and cell adhesion molecules. These features have resulted in the incorporation of immunoglobulin domains into many hundreds of cell surface molecules. Recently three major advances have been made in understanding immunoglobulin receptors. One is the recognition that their intracellular binding partners are likely to link to multiple cell surface molecules, allowing cross-talk or oligomeric complex formation. A second, but related phenomenon, is their participation in cis-interactions on the extracellular surface that regulate signaling or adhesion. The third is the dramatic ability to form dozens to thousands of different isoforms via alternative splicing. Although antibodies may have been the first example of immunoglobulin-domain-containing proteins using cis-interactions to form receptor like molecules, and the grandest instance of diversity production from limited genetic material, these are clearly old ideas in this superfamily.
Brümmendorf
T
T
Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, D-13092 Berlin, Germany. brue@mdc-berlin.de
Lemmon
V
V
D017398:Alternative Splicing; D000818:Animals; D001369:Axons / Q000502:physiology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002966:Clathrin / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007365:Intercellular Junctions / Q000378:metabolism; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics; D011971:Receptors, Immunologic / Q000378:metabolism; D000097905:Roundabout Proteins
D015815:Cell Adhesion Molecules; D002966:Clathrin; D004268:DNA-Binding Proteins; D007136:Immunoglobulins; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D011506:Proteins; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; C110833:DSCAM protein, human; C092744:ENA-VASP proteins