8.A.54 The Integrin (Integrin) Family
Integrins are transmembrane receptors that mediate cell-cell and cell-extracellular matrix interactions, which regulate numerous intracellular signals and biological functions under physiological conditions. They interlink the nucleus and plasma membrane, control tumor cell growth and progression, and determine cell motility (Madrazo et al. 2017). They play important roles in cell-cell interactions, for example, promoting fusion of sperm and egg cells during mammalian fertilization (Klinovska et al. 2014). Integrin
alpha-1/beta-1 is a receptor for laminin and collagen. It recognizes
the proline-hydroxylated sequence G-F-P-G-E-R in collagen. They are involved in
anchorage-dependent, negative regulation of EGF-stimulated cell growth.
Integrins alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta-1 and alpha-11/beta-1 are receptors for collagen. Integrins alpha-1/beta-1 and alpha-2/beta-2 recognize the proline-hydroxylated sequence G-F-P-G-E-R in collagen. Integrins alpha-2/beta-1, alpha-3/beta-1, alpha-4/beta-1, alpha-5/beta-1, alpha-8/beta-1, alpha-10/beta-1, alpha-11/beta-1 and alpha-V/beta-1 are receptors for fibronectin. Alpha-4/beta-1 recognizes one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. Integrin alpha-5/beta-1 is a receptor for fibrinogen.
Integrin alpha-1/beta-1as well as alpha-2/beta-1, alpha-6/beta-1 and alpha-7/beta-1 are receptors for lamimin. Integrin alpha-4/beta-1 is a receptor for VCAM1. It recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-9/beta-1 is a receptor for VCAM1, cytotactin and osteopontin. It recognizes the sequence A-E-I-D-G-I-E-L in cytotactin. Integrin alpha-3/beta-1 is a receptor for epiligrin, thrombospondin and CSPG4. Alpha-3/beta-1 may mediate with LGALS3 the stimulation by CSPG4 of endothelial cells migration. Integrin alpha-V/beta-1 is a receptor for vitronectin. Beta-1 integrins recognize the sequence R-G-D in a wide array of ligands. Isoform 2 interferes with isoform 1 resulting in a dominant negative effect on cell adhesion and migration. Integrin alpha-3/beta-1 provides a docking site for FAP (seprase) at invadopodia plasma membranes in a collagen-dependent manner and hence may participate in the adhesion, formation of invadopodia and matrix degradation processes, promoting cell invasion.
Binding of tauroursodeoxycholate (TUDC) to alpha5beta1-integrin, the beta1-integrin subunit becomes activated through a conformational change, thereby triggering integrin signaling. This triggers choleresis through a coordinated insertion of the sodium-taurocholate cotransporting polypeptide (TC# 2.A.28.1.2) into the basolateral membrane and of the bile salt export pump (TC# 3.A.1 201.2) into the canalicular membrane (Häussinger and Kordes 2017). The integrin β1 tail plays a key role in regulating the composition and function of tight and adherens junctions that define the paracellular transport properties of terminally differentiated renal proximal tubule epithelial cells (Elias et al. 2014).
Integrins are adhesion receptors on the cell surface that enable cells to respond to their environment. Most integrins are heterodimers, comprising alpha and beta type I transmembrane glycoprotein chains with large extracellular domains and short cytoplasmic tails. Integrins deliver signals through multiprotein complexes at the cell surface, which interact with cytoskeletal and signaling proteins to influence gene expression, cell proliferation, morphology, and migration (Siegers 2018).