Atypical structure and function of integrin α_Vβ₈

Abstract

Integrins are heterodimeric transmembrane proteins that play important roles in various biological processes. Most integrins serve as adhesion molecules and transmit bidirectional signaling across the cell membrane through global conformational changes from the bent closed to the extended open conformation. However, integrin β8 is distinctive in structure and function. Its cytoplasmic domain lacks the conserved protein‐binding sequence, which is important in transmitting inside‐out signals, suggesting that integrin β8 may have a different activation mechanism or lack such signaling. In addition, the ligand‐binding or activating metal ion Mn2+ does not induce a global conformational change in integrin β8. It may have only one conformation, that is, an extended, closed conformation, but with high affinity for ligands under physiological conditions, and is, therefore, considered an atypical integrin member. The extended structure and high ligand‐binding affinity of integrin αvβ8 make it ideal for encountering and binding ligands expressed on an opposing cell or in the extracellular matrix. In this review, we summarize the progress in integrin β8 research with a focus on its distinctive function and structure among integrin members.

YAP Inactivation by Soft Mechanotransduction Relieves MAFG for Tumor Cell Dedifferentiation

“…S2 A and B). Notably, unlike other members, β8 is unique, because (a) it only binds αv to form a heterodimer [ 27 ], and (b) its cytoplasmic domain is unlikely to augment cell spreading and adhesion for cell differentiation [ 28 ]. We therefore used CRISPR/cas9 to knock out β8 and seeded β8 −/− stiff cells into 90-Pa fibrin gels.…”

“…Next, we investigated how β8-transduced mechanical signal inactivated RhoA. Although integrin β commonly contains NPXY motifs, the β8 cytoplasmic domain is divergent and lacks these motifs [ 27 , 33 ]. Kindlin 2, an NPXY motif-interacting cytoskeletal protein, promotes YAP activation [ 34 ].…”

Crosstalk among podocytes, glomerular endothelial cells and mesangial cells in diabetic kidney disease: an updated review

“…Integrin αvβ8, with TGF-β as its primary ligand, is involved in cellular interactions between MCs and GECs. This integrin plays a central role in connecting extracellular ligands with the intracellular cytoskeleton, facilitating bidirectional signal transmission across the cell membrane [ 139 ]. Integrin αvβ8 is abundantly expressed in the kidney and has been found to be protective for the glomerular structure and function during the development of DKD.…”

The role of integrin beta in schizophrenia: a preliminary exploration

“…Classification by function 61 Distribution of integrin β in the cerebral cortex Phenotypes of integrin β deficient mice β1…”