Featured
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Integrin β1 controls VE-cadherin localization and blood vessel stability
The role of integrin β1 in angiogenesis is poorly understood. Here, the authors show that integrin β1 regulates murine angiogenesis and adherens junction integrity by controlling VE-cadherin localization, myosin light chain phosphorylation and the function of the Rap1/MRCK and Rho/Rho-kinase pathways.
- Hiroyuki Yamamoto
- , Manuel Ehling
- & Ralf H. Adams
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| Open AccessDefining the phospho-adhesome through the phosphoproteomic analysis of integrin signalling
Protein phosphorylation is known to play an important role in cell adhesion signalling. Robertson et al. present a proteomic resource mapping the phosphorylation states of proteins isolated from adhesion complexes and, taking advantage of this data set, show that the cell cycle kinase CDK1 may influence cell adhesion.
- Joseph Robertson
- , Guillaume Jacquemet
- & Martin J. Humphries
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| Open AccessEndothelial destabilization by angiopoietin-2 via integrin β1 activation
Angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) have opposing effects on vascular stability through their receptor Tie2, but there is evidence for Tie2-independent functions of Ang2. Here, Hakanpaa et al.show that Ang2 directly activates β1-integrin, leading to rearrangement of the actin cytoskeleton and decreased VE-cadherin in cell–cell junctions.
- Laura Hakanpaa
- , Tuomas Sipila
- & Pipsa Saharinen
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| Open AccessA proteomic approach reveals integrin activation state-dependent control of microtubule cortical targeting
Integrins are activated by many extracellular cues and respond by assembling diverse signalling complexes. Byron et al.use activation state-specific antibodies to proteomically characterize these complexes, and provide insight into integrin-dependent microtubule stabilization.
- Adam Byron
- , Janet A. Askari
- & Martin J. Humphries
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Conformational activation of talin by RIAM triggers integrin-mediated cell adhesion
Integrins are activated by binding to the cytoskeletal adaptor talin, but the mechanisms guiding activation are unclear. Here Yang et al.show that the Rap1 effector RIAM binds to the integrin-binding head of talin to promote integrin activation, perhaps by sterically interfering with talin autoinhibition.
- Jun Yang
- , Liang Zhu
- & Jun Qin
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DNA-based digital tension probes reveal integrin forces during early cell adhesion
Imaging mechanical tension experienced by single adhesion molecules in living cells remains a significant challenge. Zhang et al.design fluorescent probes based on DNA hairpins that can be programmed to reversibly report specific force levels generated by individual integrin molecules in a digital manner.
- Yun Zhang
- , Chenghao Ge
- & Khalid Salaita
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Integrin-linked kinase mediates force transduction in cardiomyocytes by modulating SERCA2a/PLN function
The transduction of mechanical forces into signals that alter cardiac contractility is important for heart function. Here the authors show that integrin-linked kinase acts as a mechanosensor in cardiomyocytes, and affects cardiac contractility by regulating SERCA-2a and phospholamban.
- Alexandra Traister
- , Mark Li
- & John G. Coles
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Knockdown and knockout of β1-integrin in hepatocytes impairs liver regeneration through inhibition of growth factor signalling
Integrin signalling has been implicated in liver regeneration but the molecular processes are not well understood. Here the authors show that β1-integrin is required for liver regeneration and that its absence impairs ligand-induced activation of the epidermal growth factor receptor in mice.
- Tobias Speicher
- , Beat Siegenthaler
- & Sabine Werner
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| Open AccessIntegrin CD11b positively regulates TLR4-induced signalling pathways in dendritic cells but not in macrophages
The signalling pathways that confer differences in the responses of dendritic cells and macrophages to LPS remain poorly understood. Here, Ling et al.report that the integrin C11b is required for LPS-induced TLR4 trafficking and signalling in dendritic cells but not in macrophages.
- Guang Sheng Ling
- , Jason Bennett
- & Marina Botto
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Integrin CD11b negatively regulates BCR signalling to maintain autoreactive B cell tolerance
Polymorphisms in the integrin gene CD11bare associated with susceptibility to systemic lupus erythematosus, but how this relates to the function of this integrin has not been fully investigated. Here, the authors report that CD11b has a role in the intrinsic maintenance of autoreactive B cell tolerance by regulating BCR signalling.
- Chuanlin Ding
- , Yunfeng Ma
- & Jun Yan
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Klf5 controls bone marrow homing of stem cells and progenitors through Rab5-mediated β1/β2-integrin trafficking
Klf5 is a transcription factor that regulates self-renewal of pluripotent stem cells. Here the authors test the function of Klf5 in somatic stem cells, and discover that it controls stem cell homing and adhesion by regulating endocytosis of beta integrins.
- E. Taniguchi Ishikawa
- , K. H. Chang
- & J. A. Cancelas
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A combinatorial extracellular matrix platform identifies cell-extracellular matrix interactions that correlate with metastasis
Interactions of cells with extracellular matrix are important in normal physiology and cancer metastasis. Here, an extracellular matrix molecule array is developed and used to show that conserved changes in adhesive properties are associated with metastasis, including binding to fibronectin in combination with galectin-3, galectin-8 or laminin.
- Nathan E. Reticker-Flynn
- , David F. Braga Malta
- & Sangeeta N. Bhatia
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Mst1 regulates integrin-dependent thymocyte trafficking and antigen recognition in the thymus
Autoreactive T cells are eliminated as they encounter self-antigens during transit through the thymus. Uedaet al. reveal that mice lacking the Hippo homologue Mst1 develop autoimmunity as a result of impaired integrin-dependent T cell migration through this negatively selective niche.
- Yoshihiro Ueda
- , Koko Katagiri
- & Tatsuo Kinashi