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

alpha nu beta 8 integrin is highly expressed in the vertebrate CNS, and mice lacking the alpha nu or beta 8 genes develop cerebral hemorrhage due to defective interactions between blood vessels and alpha nu beta 8-expressing neural cells. Although alpha nu beta 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 alpha nu beta 8 to regulate CNS development. Here we identify Band 4.1B as an intracellular factor that interacts selectively with the beta 8 cytoplasmic tail. The association with alpha nu beta 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 beta 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 alpha nu beta 8-Band 4.1 interactions in the development and maintenance of the CNS.