An interaction between αvβ8 integrin and Band 4.1B via a highly conserved region of the Band 4.1 C-terminal domain

Abstract

␣v␤8 integrin is highly expressed in the vertebrate CNS, and mice lacking the ␣v or ␤8 genes develop cerebral hemorrhage due to defective interactions between blood vessels and ␣v␤8-expressing neural cells. Although ␣v␤8 binds many of the same extracellular matrix protein ligands as other integrins, very little is known about the intracellular signal transduction events used by ␣v␤8 to regulate CNS development. Here we identify Band 4.1B as an intracellular factor that interacts selectively with the ␤8 cytoplasmic tail. The association with ␣v␤8 occurs via the band 4.1B C-terminal domain, a region highly conserved among the various Band 4.1 family members. Indeed, we show that ␤8 integrin interacts directly with the C-terminal domains of several Band 4.1 proteins and colocalizes with them in cultured astrocytes and in the brain. These data identify a previously uncharacterized interaction between an integrin and Band 4.1 family members and suggest an important functional role for ␣v␤8 -Band 4.1 interactions in the development and maintenance of the CNS.central nervous system ͉ extracellular matrix ͉ intracellular signal transduction

Lack of Protein 4.1G Causes Altered Expression and Localization of the Cell Adhesion Molecule Nectin-Like 4 in Testis and Can Cause Male Infertility

“…While 4.1G has been shown to bind metabotropic glutamate receptor (19), adenosine receptor (20), and parathyroid hormone receptor (36) plays an important role in linking the paranodal and juxtaparanodal adhesion complexes to the axonal cytoskeleton by interacting with Caspr and Caspr2 (12). The binding of members of the protein 4.1 family to other adhesion molecules has also been reported, such as the binding of 4.1B to the beta 8 integrin (24) and TSLC1 (51) and the binding of 4.1N to nectin-like 1 (53). Here, we show that 4.1G binds to the adhesion molecule NECL4 and that lack of 4.1G in testis resulted in the significantly decreased expression of NECL4 and the subsequent impairment of cell-cell contact between Sertoli cells and germ cells.…”

Protein Tyrosine Phosphatase-PEST and β8 Integrin Regulate Spatiotemporal Patterns of RhoGDI1 Activation in Migrating Cells

“…All experimental animal procedures were reviewed and approved by the Institutional Animal Care and Use Committee at the University of Texas M. D. Anderson Cancer Center. Astrocytes were cultured from the cerebral cortices of wild-type or ␤8 Ϫ/Ϫ newborn pups and propagated on laminincoated dishes, as described previously (32). Given the limited growth of primary astrocytes in culture, we immortalized cells as described previously (33).…”

Atypical interactions of integrin α V β 8 with pro-TGF-β1

“…The ability of pro-TGF-β1 to induce the open headpiece conformation of α V β 6 and not α V β 8 correlates with higher affinity binding with α V β 6 in Mg 2+ and greater augmentation by Mn 2+ of affinity with α V β 6 than α V β 8 . Finally, the metal ion Mn 2+ has a more complex effect on ligand binding by α V β 8 than by α V β 6 .…”

“…Evidence is mounting that activation of most integrins requires force exertion by the actin cytoskeleton and resistance by the ligand to stabilize the extended-open integrin conformation compared with the bent-closed and extended-closed conformations (11,28,29). As α V β 8 couples to a distinct type of cytoskeletal network through the DAL-1/Band 4.1B adaptor (6), it may either not be subjected to and regulated by cytoskeletal force or be subjected to force of a different magnitude than applied by the actin cytoskeleton. Our studies provide a quantitative framework for comparisons among integrins that are activated by distinctive cellular mechanisms.…”

“…Almost all integrins link to the actin cytoskeleton through talin and kindlin-binding motifs in their β-subunit cytoplasmic domains and thus provide traction for cell migration. The only exceptions are integrin α V β 8 , which binds through its β 8 -subunit to differentially express in adenocarcinoma of the lung (DAL-1, also known as Band 4.1B), and integrin α 6 β 4 , which links through its β 4 -subunit to intermediate filaments (6).…”