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Cell Migration: Integrating Signals from Front to Back
TLDR
The mechanisms underlying the major steps of migration and the signaling pathways that regulate them are described, and recent advances investigating the nature of polarity in migrating cells and the pathways that establish it are outlined. Expand
The final steps of integrin activation: the end game
TLDR
Recent progress provides insight into the structure of integrin transmembrane domains, and reveals how the final steps of Integrin activation are mediated by integrin-binding proteins such as talins and kindlins. Expand
Talin Binding to Integrin ß Tails: A Final Common Step in Integrin Activation
TLDR
It is reported that specific binding of the cytoskeletal protein talin to integrin β subunit cytoplasmic tails leads to the conformational rearrangements of integrin extracellular domains that increase their affinity. Expand
Structural Basis of Integrin Activation by Talin
TLDR
The structural basis of talin's unique ability to activate integrins is revealed, an interaction that could aid in the design of therapeutics to block integrin activation is identified, and engineering of cells with defects in the activation of multiple classes of integrin is enabled. Expand
RIAM Activates Integrins by Linking Talin to Ras GTPase Membrane-targeting Sequences*
TLDR
It is shown that MRL proteins function as scaffolds that connect the membrane targeting sequences in Ras GTPases to talin, thereby recruiting talin to the plasma membrane and activating integrins. Expand
Src kinase activation by direct interaction with the integrin β cytoplasmic domain
TLDR
The results invoke a model whereby Src is primed for activation by direct interaction with an integrin β tail, and integrin clustering stabilizes activated Src by inducing intermolecular autophosphorylation. Expand
KRIT-1/CCM1 is a Rap1 effector that regulates endothelial cell–cell junctions
TLDR
Rap1 increases KRIT-1 targeting to endothelial cell–cell junctions where it suppresses stress fibers and stabilizes junctional integrity, and decreases the ability of Rap1 to stabilize endothelial junctions associated with increased actin stress fibers. Expand
The Talin Head Domain Binds to Integrin β Subunit Cytoplasmic Tails and Regulates Integrin Activation*
TLDR
It is reported that an integrin-binding site is localized within the N-terminal talin head domain, which binds to integrins to form a link to the actin cytoskeleton and can thus regulate integrin function. Expand
Robo4 stabilizes the vascular network by inhibiting pathologic angiogenesis and endothelial hyperpermeability.
TLDR
A previously unknown function for Robo receptors in stabilizing the vasculature is defined and it is suggested that activating Robo4 may have broad therapeutic application in diseases characterized by excessive angiogenesis and/or vascular leak. Expand
Integrin cytoplasmic domain-binding proteins.
TLDR
This work has shown that through interaction with the cytoskeleton, signaling molecules, and other cellular proteins, integrin cytoplasmic domains transduce signals from both the outside and inside of the cell and regulate integrin-mediated biological functions. Expand
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