Extracellular Matrix News Volume 8.24 | Jun 22 2017

TOP STORY

Tubular Clathrin/AP-2 Lattices Pinch Collagen Fibers to Support 3D Cell Migration

Scientists analyzed the dynamics of clathrin-coated pits in cells migrating in a 3D environment of collagen fibers. Clathrin/adaptor protein 2 (AP-2) lattices pinched collagen fibers by adopting a tube-like morphology and regulated adhesion to fibers in an endocytosis-independent manner. During migration, tubular clathrin/AP-2 lattices stabilized cellular protrusions by providing anchoring points to collagen fibers. [Science] Abstract

(Ranked by impact factor of the journal)

Interaction of Reactive Astrocytes with Type I Collagen Induces Astrocytic Scar Formation through the Integrin–N-Cadherin Pathway after Spinal Cord Injury

The authors found that type I collagen was highly expressed in the spinal cord during the scar-forming phase and induced astrocytic scar formation via the integrin–N-cadherin pathway. In a mouse model of spinal cord injury, pharmacological blockade of reactive astrocyte–type I collagen interaction prevented astrocytic scar formation, which lead to improved axonal regrowth and better functional outcomes. [Nat Med] Abstract

Laminin 211 Inhibits Protein Kinase A in Schwann Cells to Modulate Neuregulin 1 Type III-Driven Myelination

Investigators used a series of epistasis experiments to show that laminin α2β1γ1 (Lm211) modulates neuregulin signaling to ensure the correct timing and amount of myelination. They provide evidence that excessive protein kinase A activation amplifies promyelinating signals downstream of neuregulin, including direct activation of the neuregulin receptor ErbB2 and its effector Grb2-Associated Binder-1, thereby elevating the expression of the key transcription factors Oct6 and early growth response protein 2. [PLoS Biol] Full Article

A Strong Contractile Actin Fence and Large Adhesions Direct Human Pluripotent Colony Morphology and Adhesion

Researchers imaged human pluripotent stem cells at the cell-ECM interface with total internal reflection fluorescence microscopy and discovered that adhesions at the colony edge were exceptionally large and connected by thick ventral stress fibers. The actin fence encircling the colony was found to exert extensive Rho-ROCK-myosin-dependent mechanical stress to enforce colony morphology, compaction, and pluripotency and to define mitotic spindle orientation. [Stem Cell Reports] Full Article | Graphical Abstract

Fibronectin Promotes Directional Persistence in Fibroblast Migration through Interactions with Both Its Cell-Binding and Heparin-Binding Domains

The authors showed that high directional persistence necessitates a combination of the cell-binding and C-terminal heparin-binding domains of fibronectin (FN), but does not require the engagement of syndecan-4 or integrin α₄β₁. FN treatment with various fixation agents indicated that associated changes in fibroblast motility were due to biochemical changes, rather than alterations in its physical state. [Sci Rep] Full Article

Aging-Associated Modifications of Collagen Affect Its Degradation by Matrix Metalloproteinases

Scientists found a reduced collagenolysis in mineralized and advanced glycation end-product-modified collagen fibers when compared to native fibrillar collagen. Matrix metalloproteinase (MMP) digestion led to a reduction in the mechanical strength of native and modified collagen fibers. Successive fiber degradation with MMPs and the cysteine-dependent collagenase, cathepsin K, resulted in their complete degradation. [Matrix Biol] Abstract

Mir-155 Is Overexpressed in Systemic Sclerosis Fibroblasts and Is Required for NLRP3 Inflammasome-Mediated Collagen Synthesis during Fibrosis

Researchers investigated whether miR-155 played a role in systemic sclerosis (SSc) and if its expression was dependent on inflammasome activation. miR-155 was significantly increased and the highest expressing miRNA in SSc lung fibroblasts. In the absence of miR-155, inflammasome-mediated collagen synthesis could not be induced but was restored when miR-155 was expressed in miR-155-deficient fibroblasts. [Arthritis Res Ther] Full Article

Stretch-Dependent Changes in Molecular Conformation in Fibronectin Nanofibers

The authors developed a modified surface-initiated assembly technique to engineer fibronectin (FN) nanofibers that they could uniaxially stretch to more than seven-fold extensions and subsequently immobilize them in the stretched state for high resolution atomic force microscopy imaging. Using this approach, they analyzed how the nanostructure of FN molecules within the nanofibers changed with stretch. [Biomater Sci] Abstract | Graphical Abstract

Inhibition of MMP-2 and MMP-9 Decreases Cellular Migration, and Angiogenesis in In Vitro Models of Retinoblastoma

Investigators compared matrix metalloproteinases-2 and -9 (MMP-2, -9) activity in two well-studied retinoblastoma cell lines: Y79, which exhibits high metastatic potential and Weri-1, which has low metastatic potential. Their results showed that both inhibitors had differential effects on the two cell lines, significantly reducing migration in the metastatic Y79 cell line and greatly affecting the viability of Weri-1 cells. [BMC Cancer] Full Article

Effects of Omega-3 on Matrix Metalloproteinase-9, Myoblast Transplantation and Satellite Cell Activation in Dystrophin-Deficient Muscle Fibers

Scientists tested the hypothesis that omega-3 affects metalloproteinase 9 (MMP-9) and thereby benefits muscle regeneration and myoblast transplantation in the mdx mouse. They observed that omega-3 reduces MMP-9 gene expression and improves myoblast engraftment, satellite cell activation, and muscle regeneration by mechanisms involving, at least in part, the regulation of macrophages. [Cell Tissue Res] Abstract

The Roles of Integrin αvβ6 in Cancer

The authors provide an overview of the current the understanding of the roles and underlying mechanisms of integrin αvβ6 in tumors. The common links as well as discrepancies between independent studies are discussed. [Cancer Lett] Abstract

Talking Over the Extracellular Matrix: How do Cells Communicate Mechanically?

Only recently, a new mode of cell communication was elucidated: mechanical communication through the ECM. Researchers review several examples of mechanical communication, discuss their unique properties, and comment on the major challenges facing the field. [Semin Cell Dev Biol] Abstract | Graphical Abstract

Formation and Remodeling of the Brain Extracellular Matrix in Neural Plasticity: Roles of Chondroitin Sulfate and Hyaluronan

The authors review recent progress in understanding of the molecular basis of organization and remodeling of the brain ECM, and the involvement of several types of experience-dependent neural plasticity. [Biochim Biophys Acta] Abstract

Visit our reviews page to see a complete list of reviews in the extracellular matrix research field.

Chi-Med Initiates a Phase I/II Clinical Trial of Novel FGFR Inhibitor HMPL 453 in China

Hutchison China MediTech Limited (Chi-Med) initiated a Phase I/II clinical trial of HMPL-453 in China. HMPL-453 is a novel, highly selective and potent small molecule inhibitor targeting fibroblast growth factor receptor (FGFR). [Hutchison China MediTech Limited] Press Release

Therachon Receives EMA and FDA Orphan Drug Designation for TA-46 for Achondroplasia

Therachon AG announced that the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) have granted Orphan Drug Designation to TA-46 for the treatment of patients with achondroplasia, the most common form of short-limbed dwarfism. [Therachon AG] Press Release

University of Tokyo Scientist Hit by Anonymous Allegations Fights Back

Anonymous allegations of questionable data and images in 22 papers by six prominent groups at the prestigious University of Tokyo prompted the school to set up an investigating committee. Now, even before the panel completes its investigation, one of the accused researchers has mounted a staunch defense of his work. [ScienceInsider] Editorial

China Cracks Down on Fake Peer Reviews

The Chinese government is going on the offensive against scientists who dupe journals by creating fraudulent reviews of submitted papers. A coalition of agencies led by the science ministry announced that the government would suspend the grants of researchers involved in such fraud, which surfaced earlier this year when a cancer journal retracted 107 research papers from Chinese authors. [Nature News] Editorial

Strengthened US Sanctions on Cuba Disappoint Scientists

US President Donald Trump announced that he would strengthen travel and trade restrictions against Cuba, reversing his predecessor’s attempts to normalize relations with the country. The move is a blow to scientists who hoped that former president Barack Obama’s push to relax US restrictions on Cuba would make it easier for researchers there to travel and to collaborate with colleagues in the United States. [Nature News] Editorial

Macron Consolidates Electoral Victory

The party of France’s recently elected president won an absolute majority in its first general elections, with an agenda that included strong support for research. [Nature News] Editorial

NEW Seven Lakes Proteoglycans Conference
September 10-14, 2017
Varese, Italy

Visit our events page to see a complete list of events in the community.

NEW Pharmacology Scientist – Matrix Biology (Symic Bio, Inc.)

NEW Postdoctoral Position – Molecular Genetics (University of Illinois College of Medicine)

NEW Director Position – Stem Cell Biology and Regenerative Medicine (University of Illinois College of Medicine in Chicago)

NEW Postdoctoral Fellow – Gene Regulation in Stem Cells and Tissue Regeneration (Northwestern University)

NEW Assistant Professor – Stem Cell and Regenerative Biology (Harvard University)

Postdoctoral Fellowship – Tissue Fibrosis (University of California, San Francisco)

Group Leaders – Multiple Areas (French National Center for Scientific Research)

Part Time Faculty – Developmental Biology (Boston College Biology Department)

Postdoctoral Fellow – Proteoglycan Remodeling (University of Alberta)

Postdoctoral Research Fellow – Tendon and Connective Tissue Biology (Weill Cornell Medical College)

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