Integrins and their ligands.
Integrins are expressed on almost every cell type and are responsible for the linkage of the extracellular matrix with the cytoskeleton. In this review I have focused on the intra- and extracellular proteins that bind to integrins. Although many integrins bind to the same extracellular ligand, they mostly recognize different sites on these ligands. Some integrins interact with the same site but then there are requirements for different additional sequences to obtain high affinity. By modulating the expression and activity of integrins in the plasma membrane, cells can adapt their capacity of binding to the matrix. How integrins become activated is as yet not clear, but interaction with other proteins or lipids may be critical. Binding to ligands could also be modulated by alternative splicing of mRNAs for ligand binding sites in the extracellular domain. In Drosophila, the mRNA for the extracellular domain of the PS2 integrin is spliced near a site implicated in ligand binding. In humans, however, there are no indications that alternative splicing contributes to the regulation of function of the extracellular domain of integrins. The only splice variant of the extracellular domain of an integrin identified so far concerns are alpha subunit of the alpha IIb beta 3 complex, but the splicing occurs in a region that has not been implicated in cell adhesion. There is also no evidence as yet that integrin function can be modulated by alternative splicing of mRNA for the cytoplasmic domain of integrin subunits. However, the loss of function seen with some deletion mutants of the cytoplasmic domains of integrin subunits suggests that such a mechanism may well exist. In a different way the binding capacity of a given cell can be influenced by regulating the expression of its ligand or by alternative mRNA splicing of sequences encoding the cell binding domain in their ligands. In the case of fibronectin, the mRNA for one of the integrin binding sites is subject to alternative splicing. The mRNAs for the three chains of laminin appear not to be subject to alternative splicing but, by combining different variant chains of laminin, isoforms can be generated which may have different affinities for integrins. Binding of cells to the matrix therefore does not only depend on the expression and activity of the correct integrin but also of the correct variant of the ligand.(ABSTRACT TRUNCATED AT 400 WORDS)
Sonnenberg
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The Netherlands Cancer Institute, Division of Cell Biology, Amsterdam.
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D006801:Humans; D016023:Integrins / Q000737:chemistry / Q000502:physiology*; D008024:Ligands; D008969:Molecular Sequence Data; D009842:Oligopeptides
D016023:Integrins; D008024:Ligands; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid