Integrins are a large family of trasmembrane proteins involved in cell adhesion and form a link between the intracellular cyskeletal proteins and extracellular matrix proteins. Integrins exist as heterodimers consisting of alpha and beta subunits. In addition to cell adhesion these integrin complexes play key roles in diverse processes such as signal transduction, cell migration, proliferation, differentiation, and apoptosis. Integrins consist of three domains: the extracellular domain, the transmembrane domain, and the cytoplasmic tail. The large globular extracellular domain is responsible for ligand binding while the transmembrane region is a single-pass α-helix. The cytoplasmic tails are short unstructured regions that form salt bridges between alpha and beta proteins as well as interact with adaptor proteins that link to the cytoskeleton. Integrin complexes are able to signal bidirectionally. Ligand binding on the outside of the cell can trigger an intracellular response such as cytoskeleton reorganization. Additionally intracellular signals can trigger a conformational change of the extracellular domain to expose or activate a ligand binding site. Integrin beta-1, also known as CD29, plays diverse signaling roles in normal development and in disease. In particular integrin beta-1 activation has been shown to regulate the transition from cell dormancy to metastasis.
In addition to contributing to metastasis Pillozzi et al. demonstrated integrin beta-1 complexes can also participate in chemotherapy resistance in acute lymphoblastic leukemia (1). They used the integrin beta-1 antibody in immunoprecipitation experiments to characterize the protein complex that confers chemotherapy resistance. This complex contains hERG1, integrin beta-1, and CXCR4 and can initiate prosurvival signals and drug resistance. The Shapiro group at the University of Connecticut investigated the role prostate specific membrane antigen (PSMA) in integrin signaling during endothelial invasion and angiogenesis (2). Interestingly treatment with the integrin beta-1 antibody is able to artificially induce adhesion of integrin to its substrate. The researchers used the integrin beta-1 antibody as a tool to induce integrin signaling and were able to bypass the requirement of PSMA for endothelial invasion. This experiment helped demonstrate PSMA participates in cell adhesion and ultimately angiogenesis by inducing the initial adhesion steps of integrin to its substrate. This study demonstrated a novel use of the integrin beta-1 antibody by using it as a tool to artificially manipulate their experimental system. The Nusrat group at Emory University investigated the regulation of cell adhesion during wound healing in intestinal epithelia (3). They had previously identified the actin binding protein annexin A2 was up-regulated during wound closure. In this study they used the integrin beta-1 antibody for western blots to show annexin A2 is needed for integrin degradation. Next they used the integrin beta-1 antibody for immunohistochemistry to demonstrate annexin A2 mediates integrin internalization and localization to endosomes. By regulating the internalization and degradation integrin-based adhesion complexes annexin A2 is able to promote cell migration and wound closure.
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