An interaction between {alpha}v{beta}8 integrin and Band 4.1B via a highly conserved region of the Band 4.1 C-terminal domain.
alphavbeta8 Integrin is highly expressed in the vertebrate CNS, and mice lacking the alphav or beta8 genes develop cerebral hemorrhage due to defective interactions between blood vessels and alphavbeta8-expressing neural cells. Although alphavbeta8 binds many of the same extracellular matrix protein ligands as other integrins, very little is known about the intracellular signal transduction events used by alphavbeta8 to regulate CNS development. Here we identify Band 4.1B as an intracellular factor that interacts selectively with the beta8 cytoplasmic tail. The association with alphavbeta8 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 beta8 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 alphavbeta8-Band 4.1 interactions in the development and maintenance of the CNS.
McCarty
Joseph H
JH
Howard Hughes Medical Institute and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cook
Aaron A
AA
Hynes
Richard O
RO
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000196:embryology; D019556:COS Cells; D002543:Cerebral Hemorrhage / Q000235:genetics / Q000378:metabolism; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
D003598:Cytoskeletal Proteins; D016023:Integrins; D008565:Membrane Proteins; C028841:erythrocyte membrane band 4.1 protein; C403414:integrin alphavbeta8