Regulation of cell adhesion: a collaborative effort of integrins, their ligands, cytoplasmic actors, and phosphorylation. (2019)

• Record Type: Journal Article
• Authors: Gahmberg, Carl G.; Grönholm, Mikaela; Madhavan, Sudarrshan; Jahan, Farhana; Mikkola, Esa; Viazmina, Larisa; Koivunen, Erkki
• Is Part Of: Quarterly reviews of biophysics. Volume 52(2019)
• Publication Date: 2019
• Subjects: Cell adhesion, -- integrin, -- leukocyte, -- LFA-1, -- phosphorylation; Biophysics -- Periodicals; 571.405
• DOI: 10.1017/S0033583519000088
• Languages: English
• ISSNs: 0033-5835

Abstract

Abstract: Integrins are large heterodimeric type 1 membrane proteins expressed in all nucleated mammalian cells. Eighteen α -chains and eight β -chains can combine to form 24 different integrins. They are cell adhesion proteins, which bind to a large variety of cellular and extracellular ligands. Integrins are required for cell migration, hemostasis, translocation of cells out from the blood stream and further movement into tissues, but also for the immune response and tissue morphogenesis. Importantly, integrins are not usually active as such, but need activation to become adhesive. Integrins are activated by outside-in activation through integrin ligand binding, or by inside-out activation through intracellular signaling. An important question is how integrin activity is regulated, and this topic has recently drawn much attention. Changes in integrin affinity for ligand binding are due to allosteric structural alterations, but equally important are avidity changes due to integrin clustering in the plane of the plasma membrane. Recent studies have partially solved how integrin cell surface structures change during activation. The integrin cytoplasmic domains are relatively short, but by interacting with a variety of cytoplasmic proteins in a regulated manner, the integrins acquire a number of properties important not only for cell adhesion and movement, but also for cellular signaling. Recent work has shown that specific integrin phosphorylations play pivotal roles in the regulation of integrin activity. Our purpose in this review is to integrate the present knowledge to enable an understanding of how cell adhesion is dynamically regulated.