Relevance of Autophagy Induction by Gastrointestinal Hormones: Focus on the Incretin-Based Drug Target and Glucagon

Kanasaki, Keizo; Kawakita, Emi; Koya, Daisuke

The interaction with the extracellular matrix is an important determinant of cell fate. Integrins are glycoproteins that play vital roles in cell-cell or cell-matrix interactions through αβ heterodimers. Eighteen α and eight β subunits of integrins are known, and each of them displays diverse ligand binding and signaling properties (Pozzi and Zent, 2011) . Integrin subunits consist of an extracellular domain that is important for their ligand binding properties and contains a transmembrane domain and a short cytoplasmic tail, which could interact with diverse cytosolic and transmembrane proteins by consisting a focal adhesion complex (with the exception of β4) (Pozzi and Zent, 2003) . Integrins display physical interaction with several extracellular matrix (ECM) glycoproteins (such as collagens, fibronectins, and laminins) and cellular receptors (Plow et al., 2000; Hynes, 2002) . Integrins are essential molecules in actin cytoskeleton remodeling and in regulating cell signals that regulate biological and cellular functions (Park et al., 2015) . Integrins display intracellular signaling through ligand binding ("outside-in" signaling) (Ratnikov et al., 2005) . Alternatively, integrins can alter their high-to low-affinity conformations, facilitating specific ligand binding ("inside-out" signaling) (Luo et al., 2007) . The activation status of integrin relies on the cell type. In most cells that adhere to the basement membrane, integrins are activated; in contrast, integrins are inactive in circulating platelets or leukocytes until they are induced by platelet aggregation or stimulated by an inflammatory response. Integrins contain neither a catalytic site nor kinase activity but play a role as a bridge between the ECM and actin cytoskeleton. Such interaction between the ECM and the actin cytoskeleton through integrins allows integrins to maintain cytoskeletal organization, cell motility and intracellular-signaling pathways such as cell survival, cell shape, cell proliferation, and angiogenesis (Arnaout et al., 2007; Luo et al., 2007) .