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Biology LibreTexts

13.6: Integrins

  • Page ID
    16175
  • The integrins have thus far been introduced as receptors for fibronectin and laminin, but it is a large family with a wide variety of substrates. For example, the focal adhesion (fig. 8) shows an an integrin receptor bound to collagen. As already discussed in the previous chapter, focal adhesions are usually transient, and seen as points of contact as fibroblasts or other migratory cells crawl on a culture dish or slide coated with ECM proteins.

    Screen Shot 2019-01-08 at 11.58.48 AM.png

    Figure 8. A focal adhesion is a dynamic point of contact formed by a cell growing on a collagen-coated dish.

    In addition to collagen, fibronectins and laminins are also potential binding partners for integrins. As table 1 shows, the diversity of subunits and combinations means that integrins are involved in a wide array of cellular processes, and can bind cell surface proteins as well as ECM.

    Table 1: Integrin receptors, their ligands and distribution.
    Subunits Ligand Distribution
    α1β1 mostly collagens, also laminin widespread
    α2β1 mostly collagens, also laminin widespread
    α4β1 fibronectin, VCAM-1 hematopoietic cells
    α5β1 fibronectin fibroblasts
    α6β1 laminin widespread
    α6β4 laminin epithelial cells
    αLβ2 ICAM-1, ICAM-2 T-lymphocytes
    αllbβ3 fibronectin, fibrinogen platelets

    With this variety, it is not surprising that not all integrins bind RGD sequences, although most do. For example, α2β1 integrins prefer YYGDLR or FYFDLR sequences, and αIIbβ3 binds both the RGD and a KQAGDV sequence strongly. Integrin activation has been shown to initiate signaling pathways, beginning focal adhesion kinase (FAK) or a few other central kinases, which control activities from cytoskeletal rearrangement to cell survival.

    Both α and β subunits are transmembrane proteins that pass through the membrane just once. Evolutionarily, they are found only in metazoan species, but they are also found in all metazoan species. All integrins but one, α6β4, connect to the actin microfilament cytoskeleton through the b subunit cytoplasmic domain. The α6β4 integrin links to the intermediate filament cytoskeleton, in part because the β4 cytoplasmic domain is very large and extends further into the cytoplasm. On the extracellular side, there is a metal ion coordination site usually occupied by Mg2+, that is necessary for ligand binding. There are also several other divalent ion binding sites, The receptor can be found in either an inactive (somewhat bent over towards the membrane) or an active state (straightened up). In the inactive state, the a subunit binds the β subunit closely preventing interaction with the cytoskeleton. However, once a subunit cytoplasmic domain, it displaces the a subunit, causing a slight separation of the two subunits and leading to activation of the receptor. In fact, integrins demonstrate what is known as “inside-out” signaling, in which a cellular signal (for example, from the signaling cascade of a growth factor) leads to alterations to the cytoplasmic domain and which shifts the conformation of the extracellular domain to an active straightened-up state in which it can more readily bind to ligands. This is why integrins are so well suited to focal adhesions and other “in motion” adhesions that must adhere and release quickly. Though recycling of receptors also happens, turning them on or off by inside-out signaling is an effective mechanism for fast movement.

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    Figure 9. Integrin receptors are composed of two polypeptides that each pass through the membrane once.

    As one might expect from an actin-linked structure, focal adhesions and their in vivo equivalents are transient, dynamic points of contact between the cell and the substrate it is crawling over. However, there are many situations in which a cell is not only stationary, it needs to be firmly attached to its substrate in order to gird itself for what- ever stressors might come to test its resolve. In these cases, the actin cytoskeleton is too ephemeral for the task.