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

αvβ5 integrin is highly expressed in the vertebrate CNS, and mice lacking the αv or β8 genes develop cerebral hemorrhage due to defective interactions between blood vessels and αvβ8-expressing neural cells. Although αvβ8 binds many of the same extracellular matrix protein ligands as other integrins, very little is known about the intracellular signal transduction events used by αvβ8 to regulate CNS development. Here we identify Band 4.1B as an intracellular factor that interacts selectively with the β8 cytoplasmic tail. The association with αvβ8 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 β8 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 αvβ8-Band 4.1 interactions in the development and maintenance of the CNS.