The integrin beta tail is required and sufficient to regulate adhesion signaling to Rac1.
Rac1 is a small Rho family GTPase that regulates changes in cell morphology associated with cell spreading and migration. Integrin-mediated adhesion is known to activate Rac1 and to regulate the interaction of Rac1 with downstream effectors. Currently, it is not clear how integrins signal Rac1 activation following cell adhesion. Integrin beta cytoplasmic domains (beta-tails) are known to be required for integrin-mediated cell spreading, and isolated beta tails expressed as tac-beta tail chimeras can inhibit cell spreading indicating that protein interactions with beta tails can regulate this process. Our recent studies demonstrated that the expression of constitutively activated Rac1 can restore cell spreading inhibited by tac beta tail chimeras, suggesting a role for Rac1 in the regulation of cell spreading by beta tails. Hence, we examined the role of beta tails in integrin activation of Rac1. By using recombinant wild-type and mutant integrin heterodimers, we demonstrate that integrin beta tails are required for adhesion to increase Rac1-GTP loading. We demonstrate that clustering tac-beta tail chimeras, on the surface of cells in suspension, activates Rac1. Thus, beta tails are not only required, but also sufficient for integrin-triggered Rac1 activation. Our findings indicate that integrin beta-tails are an important link between integrin engagement and Rac1 signaling, and that protein interactions initiated at beta tails are sufficient for integrins to regulate Rac1 activity.
Berrier
Allison L
AL
The Center for Cell Biology and Cancer Research, Albany Medical College, Albany, NY 12208, USA.
Martinez
Robert
R
Bokoch
Gary M
GM
LaFlamme
Susan E
SE
D002448:Cell Adhesion / Q000235:genetics*; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D005057:Eukaryotic Cells / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D039641:Integrin beta Chains / Q000235:genetics / Q000378:metabolism*; D008297:Male; D017434:Protein Structure, Tertiary / Q000235:genetics; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
D039641:Integrin beta Chains; D011993:Recombinant Fusion Proteins; D020830:rac1 GTP-Binding Protein