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| Open AccessCis interaction between sialylated FcγRIIA and the αI-domain of Mac-1 limits antibody-mediated neutrophil recruitment
Deposited immune complexes (IC) promote neutrophil recruitment, but the fine tuning of this process is still unclear. Here the authors show that the cis interaction of the IC receptor, FcγRIIA and CD18 integrin, Mac-1, on the neutrophil surface modulates neutrophil adhesion, with FcγRIIA sialylation specifically implicated in this interaction.
- Gurpanna Saggu
- , Koshu Okubo
- & Tanya N. Mayadas
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Article
| Open AccessMacrophage-derived netrin-1 promotes abdominal aortic aneurysm formation by activating MMP3 in vascular smooth muscle cells
Abdominal aortic aneurysms (AAA) are characterized by extensive extracellular matrix degradation. Here Hadi et al. identify a netrin-1/neogenin-based crosstalk between macrophages and vascular smooth muscle cells (VSMCs), leading to the secretion of the matrix metalloproteinase MMP-3 by VSMCs and subsequent matrix degradation in AAA lesions.
- Tarik Hadi
- , Ludovic Boytard
- & Bhama Ramkhelawon
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Article
| Open AccessDistinct contributions of tensile and shear stress on E-cadherin levels during morphogenesis
The effects of mechanical forces, generated by actomyosin contractility, on E-cadherin based cell adhesion are poorly characterized in vivo. Here, the authors report that normal stress increases E-cadherin levels, whereas shear stress reduces E-Cadherin levels, in the developing Drosophila embryo.
- Girish R. Kale
- , Xingbo Yang
- & Thomas Lecuit
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Article
| Open AccessCell metabolism regulates integrin mechanosensing via an SLC3A2-dependent sphingolipid biosynthesis pathway
Mechanical and metabolic cues contribute to regulate cell and tissue homeostasis but how they are integrated is not known. Here the authors show that the amino acid transporter and integrin coreceptor CD98hc regulates mechanical signaling downstream of integrins indirectly through regulating sphingolipid availability.
- Etienne Boulter
- , Soline Estrach
- & Chloé C. Féral
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Article
| Open AccessEngulfing cells promote neuronal regeneration and remove neuronal debris through distinct biochemical functions of CED-1
It is unclear how removal of axon debris and initiation of axon regeneration following nerve injury is co-regulated. In this study, the authors show that the extracellular domain (ECD) of the engulfment receptor, CED-1, functions as an adhesion molecule to promote axonal regeneration after injury, independent of its function in phagocytosis
- Hui Chiu
- , Yan Zou
- & Chieh Chang
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Article
| Open AccessIntegrating chemical and mechanical signals through dynamic coupling between cellular protrusions and pulsed ERK activation
Cellular ERK activation occurs as discrete pulses but their relationship to upstream Ras signaling is still under debate. Here, the authors show that Ras signaling associated with cellular protrusions triggers pulsed ERK activation, thereby enabling cells to integrate chemical and mechanical stimuli.
- Jr-Ming Yang
- , Sayak Bhattacharya
- & Chuan-Hsiang Huang
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Article
| Open AccessMyh10 deficiency leads to defective extracellular matrix remodeling and pulmonary disease
Abnormal alveolar development and homeostasis are common features of pulmonary disease. Here the authors show that Myh10 expression is reduced in emphysema patients, and that Myh10 loss of function impairs alveolar formation and lung morphogenesis via upregulation of matrix metalloproteinase activity and altered matrix remodeling.
- Hyun-Taek Kim
- , Wenguang Yin
- & Didier Y. R. Stainier
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Article
| Open AccessNon-catalytic signaling by pseudokinase ILK for regulating cell adhesion
Pseudokinase ILK is essential for dynamic communication between focal adhesion complexes and F-actin filaments. Here, the authors show that ILK regulates such communication by complexing with PINCH and Parvin to trigger F-actin filament bundling through previously unrecognized actin binding motifs in PINCH and Parvin
- Julia Vaynberg
- , Koichi Fukuda
- & Jun Qin
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Comment
| Open AccessCancer cells with trapped nuclei cut their way through the extracellular matrix
When an invading cancer cell attempts to pass through a hole in the extracellular matrix (ECM) which is too small for its nucleus, this generates physical tension. This tension is sensed by a nucleus–centrosome connection that activates trafficking of endosomal vesicles containing the matrix metalloprotease, MT1-MMP1 to the site of constraint. Recent evidence shows how focussed ECM degradation relieves the constraint and allows cancer cells to continue invading.
- Emmanuel Dornier
- & Jim C. Norman
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Article
| Open AccessGap junction protein Connexin-43 is a direct transcriptional regulator of N-cadherin in vivo
Connexins are components of gap junctions that link cells and allow intercellular communication. Here, the authors show that the Connexin 43 carboxy tail interacts with basic transcription factor-3, leading to nuclear translocation and direct regulation of N-cadherin expression and neural crest migration.
- Maria Kotini
- , Elias H. Barriga
- & Roberto Mayor
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Article
| Open AccessFrustrated endocytosis controls contractility-independent mechanotransduction at clathrin-coated structures
Cells sense mechanical properties of their environment using various cellular structures including focal adhesions. Here, the authors identify flat clathrin-coated structures (CCSs) as mechanosensitive signaling platforms that form independently of contractility and in response to substrate rigidity.
- Francesco Baschieri
- , Stéphane Dayot
- & Guillaume Montagnac
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Article
| Open AccessJunction-based lamellipodia drive endothelial cell rearrangements in vivo via a VE-cadherin-F-actin based oscillatory cell-cell interaction
During the formation of the zebrafish dorsal longitudinal anastomotic vessel, blood vessels connect in a process called anastomosis. Using live imaging, the authors here show that endothelial cell movements during blood vessel anastomosis are associated with oscillating lamellipodia-like structures, oriented in the direction of the movements and emerging at endothelial cell junctions.
- Ilkka Paatero
- , Loïc Sauteur
- & Heinz-Georg Belting
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Article
| Open AccessMonolayer surface chemistry enables 2-colour single molecule localisation microscopy of adhesive ligands and adhesion proteins
To date, the precise localisation of ligands and adhesion proteins are determined in two parallel characterization setups. Here, the authors report a self-assembled monolayer chemistry for indium tin oxide surfaces allowing single molecule localisation microscopy (SMLM) imaging of ligands and adhesion proteins in a single experiment.
- Xun Lu
- , Philip R. Nicovich
- & J. Justin Gooding
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Article
| Open AccessIntravital imaging-based analysis tools for vessel identification and assessment of concurrent dynamic vascular events
Different stimuli can induce dynamic changes in blood flow velocity, vessel diameter and permeability. Here the authors develop a multi-photon microscopy-based image analysis tool allowing the identification of vessels and the assessment of rapid changes in large vascular networks.
- Naoki Honkura
- , Mark Richards
- & Lena Claesson-Welsh
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Article
| Open AccessLaminin heparin-binding peptides bind to several growth factors and enhance diabetic wound healing
Laminins are important regulators of epidermal wound healing. Here, the authors show that laminins bind to multiple growth factors via their heparin-binding domains, and that incorporation of these domains into fibrin matrices increases growth factor retention, promoting wound healing in type 2 diabetic mouse models.
- Jun Ishihara
- , Ako Ishihara
- & Jeffrey A. Hubbell
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Article
| Open AccessProbing the gating mechanism of the mechanosensitive channel Piezo1 with the small molecule Yoda1
Piezo ion channels transduce mechanical stimuli into biological signals but the underlying mechanism has remained elusive. Here, the authors use the selective agonist Yoda1 to identify molecular determinants of Piezo activation, providing mechanistic insights into Piezo-mediated mechanotransduction.
- Jerome J. Lacroix
- , Wesley M. Botello-Smith
- & Yun Luo
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Article
| Open AccessMatrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program
Mechanical cues are known to influence endothelial cell behavior. Here Frye et al. show that lymphatic endothelial cell progenitors experience varying degrees of matrix stiffness during development, and that matrix stiffness regulates GATA2 expression to drive lymphatic vessel formation.
- Maike Frye
- , Andrea Taddei
- & Taija Mäkinen
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Article
| Open AccessCompression force sensing regulates integrin αIIbβ3 adhesive function on diabetic platelets
Diabetes is associated with an increased thrombotic response, but the mechanism is unknown. Here the authors demonstrate that compressive force activates integrin αIIbβ3 on discoid diabetic platelets and that platelet aggregates can be eliminated by PI 3-kinase inhibition, but not by anti-thrombotics aspirin or clopidogrel.
- Lining Ju
- , James D. McFadyen
- & Shaun P. Jackson
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Article
| Open AccessDesmosomal cadherin association with Tctex-1 and cortactin-Arp2/3 drives perijunctional actin polymerization to promote keratinocyte delamination
The epidermis is a multi-layered epithelium formed by the differentiation of basal cells and movement into suprabasal layers. Here the authors define a role for the desmosomal cadherin desmoglein-1 in promoting the delamination of basal cells by remodeling the actin cytoskeleton through interactions with the dynein light chain Tctex-1 and cortactin.
- Oxana Nekrasova
- , Robert M. Harmon
- & Kathleen J. Green
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Article
| Open AccessMT4-MMP deficiency increases patrolling monocyte recruitment to early lesions and accelerates atherosclerosis
Matrix metalloproteinases (MMP) are involved in vascular remodeling associated with plaque progression. Little is known about their immune regulatory role in vascular disorders. Here, the authors report that MT4-MMP-deficiency increases the recruitment of patrolling monocytes to early atherosclerotic lesions, which accelerates atherosclerosis.
- Cristina Clemente
- , Cristina Rius
- & Alicia G. Arroyo
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Article
| Open AccessSingle cell polarity in liquid phase facilitates tumour metastasis
Polarisation of metastasising cancer cells in circulation has not been investigated before. Here the authors identify single cell polarity as a distinct polarisation state of single cells in liquid phase, and show that perturbing single cell polarity affects attachment, adhesion, transmigration and metastasis in vitro and in vivo.
- Anna Lorentzen
- , Paul F. Becker
- & Mathias Heikenwalder
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Article
| Open AccessEGFL7 reduces CNS inflammation in mouse
Endothelial cells release extracellular matrix components that regulate inflammation. Here the authors demonstrate that the extracellular matrix component epidermal growth factor-like protein 7 regulates inflammation in experimental autoimmune encephalomyelitis in the mouse.
- Catherine Larochelle
- , Timo Uphaus
- & Frauke Zipp
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Article
| Open AccessVps3 and Vps8 control integrin trafficking from early to recycling endosomes and regulate integrin-dependent functions
The CORVET complex is a multi-subunit complex that regulates fusion between early endosomes. Here the authors show that the CORVET subunits Vps3 and Vps8 also regulate vesicular transport from early to recycling endosomes and are required for recycling integrins to the plasma membrane.
- Caspar T. H. Jonker
- , Romain Galmes
- & Judith Klumperman
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Article
| Open AccessSOD3 improves the tumor response to chemotherapy by stabilizing endothelial HIF-2α
Tumour vasculature influences drug delivery. Here, the authors show that SOD3 re-expression enhances doxorubicin delivery and effects through normalization of tumour vasculature via the HIF-2a/VE-cadherin pathway.
- Emilia Mira
- , Lorena Carmona-Rodríguez
- & Santos Mañes
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Article
| Open AccessControl of cell morphology and differentiation by substrates with independently tunable elasticity and viscous dissipation
Purely elastic biomimetic soft materials are used to characterize the mechanical response of cells, but do not resemble real tissues. Here the authors develop a viscoelastic solid hydrogel, based on polyacrylamide, that can be tuned to closely resemble soft tissue, and show the influence of viscous dissipation on cellular mechanical sensing.
- Elisabeth E. Charrier
- , Katarzyna Pogoda
- & Paul A. Janmey
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Article
| Open AccessThe opposing forces of shear flow and sphingosine-1-phosphate control marginal zone B cell shuttling
Marginal zone B (MZB) cells shuttle between the marginal zone and lymphoid follicle to capture and present peripheral blood antigens. Here the authors show that shear force, such as blood flow from the sinus around the follicle, is a directional cue that induces MZB migration on ICAM-1, and that S1P signaling inhibits this directional migration.
- Kerry Tedford
- , Michael Steiner
- & Klaus-Dieter Fischer
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Article
| Open AccessPolarized actin and VE-cadherin dynamics regulate junctional remodelling and cell migration during sprouting angiogenesis
The formation of new blood vessels requires both polarized cell migration and coordinated control of endothelial cell contacts. Here, Cao and colleagues describe at the sub-cellular level the cytoskeletal and cell junction dynamics regulating these processes upon VEGF-induced cell elongation.
- Jiahui Cao
- , Manuel Ehling
- & Hans Schnittler
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Article
| Open AccessDirection of actin flow dictates integrin LFA-1 orientation during leukocyte migration
Integrin αβ heterodimer cell surface receptors mediate adhesive interactions that provide traction for cell migration. Here the authors show that actin flow can orient cell surface integrins during leukocyte migration, suggesting integrin activation by cytoskeletal force.
- Pontus Nordenfelt
- , Travis I. Moore
- & Timothy A. Springer
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Article
| Open AccessInduced cortical tension restores functional junctions in adhesion-defective carcinoma cells
Cancer cells can disrupt cell-to-cell junctions, thus allowing migration and metastasis. Here starting from a chemical screening, Ito et al. reconstitute a step-by-step mechanism linking microtubule depolymerization and epithelial cell junction restoration.
- Shoko Ito
- , Satoru Okuda
- & Masatoshi Takeichi
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Article
| Open AccessStructure of Rap1b bound to talin reveals a pathway for triggering integrin activation
The transmembrane receptor integrin is activated by talin, but so far it has remained elusive how talin is recruited to the plasma membrane. Here, the authors identify the Rap1-mediated membrane-targeting mechanism for talin, present the Rap1b/talin-F0 structure and show that talin is a direct Rap1b effector.
- Liang Zhu
- , Jun Yang
- & Jun Qin
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Article
| Open AccessmDia1 senses both force and torque during F-actin filament polymerization
Formins are actin-polymerisation factors that are sensitive to force. Here the authors find that pulling force on an actin filament promoted faster actin polymerisation by the formin mDia1, and also found that the actin filament must be torsionally unconstrained, suggesting that mDia1 can also sense torque.
- Miao Yu
- , Xin Yuan
- & Jie Yan
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Article
| Open AccessNOTCH1 is a mechanosensor in adult arteries
The arterial wall is subjected to mechanical forces that modulate endothelial cell responses. Here, Mack and colleagues identify a novel role for Notch1 as a mechanosensor in adult arteries, where it ensures junctional integrity through modulation of calcium signalling and limits atherosclerosis.
- Julia J. Mack
- , Thiago S. Mosqueiro
- & M. Luisa Iruela-Arispe
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Article
| Open AccessLive imaging molecular changes in junctional tension upon VE-cadherin in zebrafish
Mechanical forces play a crucial role during morphogenesis, but how these are sensed and transduced in vivo is not fully understood. Here the authors apply a FRET tension sensor to live zebrafish and study changes in VE-cadherin tension at endothelial cell-cell junctions during arterial maturation.
- Anne Karine Lagendijk
- , Guillermo A. Gomez
- & Benjamin M. Hogan
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Article
| Open AccessQuantitative structural mechanobiology of platelet-driven blood clot contraction
Blood clot contraction is a cellular (patho)physiological process essential for wound healing, hemostasis, and thrombosis. Here, the authors describe the physical structural mechanism by which platelet filopodia pull “hand-over-hand” on fibrin fibers to compact them into bundled agglomerates.
- Oleg V. Kim
- , Rustem I. Litvinov
- & John W. Weisel
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Article
| Open AccessHedgehog mediated degradation of Ihog adhesion proteins modulates cell segregation in Drosophila wing imaginal discs
The range of Hedgehog (Hh) signalling in the Drosophila imaginal disc is limited by Hh/receptor degradation at the anterior/posterior (A/P) compartment boundary. Here, the authors show that degradation is mediated by co-receptor proteins Ihog/Boi, whose cell adhesion functions also contribute to A/P cell segregation.
- Elaine Y. C. Hsia
- , Ya Zhang
- & Xiaoyan Zheng
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Article
| Open AccessE-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning
In multi-layered epithelia tight junctions (TJ) are confined to the most suprabasal viable layer. Here the authors show that this is regulated by ubiquitously localized E-cadherin tuning junctional tension and EGFR activity to inhibit TJ formation in lower layers while promoting TJ stability in the granular layer 2.
- Matthias Rübsam
- , Aaron F. Mertz
- & Carien M. Niessen
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Article
| Open AccessApical surface supracellular mechanical properties in polarized epithelium using noninvasive acoustic force spectroscopy
Determination of apical tension, fluidity, and intercellular adhesive forces in an epithelial monolayer are currently disruptive. Here the authors present a method using acoustic force microscopy to measure changes in these parameters upon tight junction structural alterations in a MDCK monolayer.
- Alexander X. Cartagena-Rivera
- , Christina M. Van Itallie
- & Richard S. Chadwick
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Article
| Open AccessExtracellular matrix stiffness and cell contractility control RNA localization to promote cell migration
Adenomatous polyposis coli (APC) regulates the localization of some mRNAs at cellular protrusions but the underlying mechanisms and functional roles are not known. Here the authors show that APC-dependent RNAs are enriched in contractile protrusions, via detyrosinated microtubules, and enhance cell migration.
- Tianhong Wang
- , Susan Hamilla
- & Stavroula Mili
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Article
| Open AccessTyrosine dephosphorylated cortactin downregulates contractility at the epithelial zonula adherens through SRGAP1
Epithelial cell-cell adhesions are contractile junctions, but whether contractility can be down-regulated is not known. Here the authors report how tyrosine dephosphorylation of the cytoskeletal scaffold, cortactin, recruits the RhoA antagonist SRGAP1 to relax adherens junctions in response to HGF.
- Xuan Liang
- , Srikanth Budnar
- & Alpha S. Yap
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Article
| Open AccessNovel ecto-tagged integrins reveal their trafficking in live cells
Integrins are cell-surface adhesion receptors that are modulated by endo-exocytic trafficking, but existing tools to study this process can interfere with function. Here the authors develop β1 integrins carrying traceable tags in the extracellular domain; a pH-sensitive pHlourin tag or a HaloTag to facilitate dye attachment.
- Clotilde Huet-Calderwood
- , Felix Rivera-Molina
- & David A. Calderwood
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Article
| Open AccessPlanar polarized Rab35 functions as an oscillatory ratchet during cell intercalation in the Drosophila epithelium
Various stages of tissue morphogenesis involve the contraction of epithelial surfaces. Here, the authors identify the Rab GTPase Rab35 as an essential component of this contractile process, which functions as a membrane ratchet to ensure unidirectional movement of intercalating cells.
- Cayla E. Jewett
- , Timothy E. Vanderleest
- & J. Todd Blankenship
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Article
| Open AccessSorting at embryonic boundaries requires high heterotypic interfacial tension
The mechanisms that cause different cells to segregate into distinct tissues are unclear. Here the authors show in Xenopus that formation of a boundary between two tissues is driven by local tension along the interface rather than by global differences in adhesion or cortical contractility.
- Laura Canty
- , Eleyine Zarour
- & François Fagotto
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Article
| Open AccessPhysical limits to biomechanical sensing in disordered fibre networks
Cells in the connective tissue are surrounded by a heterogeneous network of biopolymers. Here, the authors investigate how such heterogeneity affects cellular mechanosensing by simulating the deformation response of experimental and modelled biopolymer networks to locally applied forces.
- Farzan Beroz
- , Louise M. Jawerth
- & Ned S. Wingreen
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Article
| Open AccessLFA-1 activates focal adhesion kinases FAK1/PYK2 to generate LAT-GRB2-SKAP1 complexes that terminate T-cell conjugate formation
The T-cell integrin LFA-1 binds ICAM-1 on antigen presenting cells to affect TCR-MHC interactions. Here the authors show detailed mechanics of how LFA-1 ligation affects T-cell conjugation to dendritic cells to regulate adhesion and de-adhesion of these cells in the context of antigen presentation.
- Monika Raab
- , Yuning Lu
- & Christopher E. Rudd
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Article
| Open AccessCMG2/ANTXR2 regulates extracellular collagen VI which accumulates in hyaline fibromatosis syndrome
Hyaline fibromatosis syndrome (HFS) is a hereditary disease characterized by nodular cutaneous lesions and joint pain. Here Bürgiet al. show that CMG2/ANTXR2 regulates collagen VI abundance, with loss-of-function mutations promoting collagen VI accumulation in HFS nodules and myometrial collagen deposition and sterility in mice, which can be rescued by depleting collagen VI.
- Jérôme Bürgi
- , Béatrice Kunz
- & F. Gisou van der Goot
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Article
| Open AccessStrength of Neisseria meningitidis binding to endothelial cells requires highly-ordered CD147/β2-adrenoceptor clusters assembled by alpha-actinin-4
Neisseria meningitidis bacteria bind to host proteins CD147 and β2-adrenergic receptor on the surface of endothelial cells. Here, Maïssa et al. show that the two proteins interact with each other forming clusters that increase the binding strength of the bacteria to endothelial cells.
- Nawal Maïssa
- , Valentina Covarelli
- & Sandrine Bourdoulous
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Article
| Open AccessACF7 regulates inflammatory colitis and intestinal wound response by orchestrating tight junction dynamics
The cytoskeleton plays a key role in cell/cell junction formation, but how the coordinated behaviour of the cytoskeleton contributes is not known. Here the authors show that actin-microtubule crosslinker ACF7 plays a key role in tight junction stabilization and wound healing in intestinal epithelium.
- Yanlei Ma
- , Jiping Yue
- & Xiaoyang Wu
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Article
| Open AccessConcerted regulation of retinal pigment epithelium basement membrane and barrier function by angiocrine factors
Establishment of the outer blood-retina barrier is a hallmark of retinal development but the contribution of choroid endothelial cells (ECs) is not known. Here the authors show in the developing mouse retina that ECs remodel the basement membrane and lead to enhanced barrier function of retinal epithelial cells.
- Ignacio Benedicto
- , Guillermo L. Lehmann
- & Enrique Rodriguez-Boulan
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Article
| Open AccessYAP regulates cell mechanics by controlling focal adhesion assembly
The transcriptional co-activator YAP is known to operate downstream of mechanical signals arising from the cell niche. Here the authors demonstrate that YAP controls cell mechanics, force development and adhesion strength by promoting the transcription of genes related to focal adhesions.
- Giorgia Nardone
- , Jorge Oliver-De La Cruz
- & Giancarlo Forte