Overview of Extracellular Matrix

Mecham, Robert P.

doi:10.1002/0471143030.cb1001s57

Cited by 139 publications

(134 citation statements)

References 94 publications

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“…To build upon what is known about SMG6 and further delineate the molecular mechanisms surrounding SMG6 activity, we established an SMG6 TFA, a comprehensive description of which can be found elsewhere (29). Full-length SMG6, mutants thereof and a fragment of LacZ serving as a control were fused to the MS2 coat protein, which in turn can be artificially tethered to a β-globin reporter mRNA containing six MS2 binding sites in its 3′-untranslated region (3′UTR) (β-globin-6-MBS; Figure 1A).…”

Section: Resultsmentioning

confidence: 99%

“…The shRNA target sequence for SMG5 was defined in (27) and the rest have been described elsewhere (28). The remainder of the pSUPuro-based knockdown procedure, cell harvesting for both protein and RNA samples (which were taken from the same sample), total RNA extraction and measurement of relative mRNA levels by quantitative reverse transcription polymerase chain reaction (RT-qPCR) was done as previously explained (29). qPCR assays have been described elsewhere (27,28), except for the TaqMan assay to measure eukaryotic green fluorescent protein (eGFP) mRNA levels that is comprised of 5′-TGAGCAAAGACCCCAACGA-3′, 5′-GGCGGCGGTCACGAA-3′ and 5′-FAM-GCGGATCACATGGTCCTGCTGG-BHQ1 -3′.…”

Section: Methodsmentioning

confidence: 99%

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A novel phosphorylation-independent interaction between SMG6 and UPF1 is essential for human NMD

et al. 2014

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Eukaryotic mRNAs with premature translation-termination codons (PTCs) are recognized and eliminated by nonsense-mediated mRNA decay (NMD). NMD substrates can be degraded by different routes that all require phosphorylated UPF1 (P-UPF1) as a starting point. The endonuclease SMG6, which cleaves mRNA near the PTC, is one of the three known NMD factors thought to be recruited to nonsense mRNAs via an interaction with P-UPF1, leading to eventual mRNA degradation. By artificial tethering of SMG6 and mutants thereof to a reporter mRNA combined with knockdowns of various NMD factors, we demonstrate that besides its endonucleolytic activity, SMG6 also requires UPF1 and SMG1 to reduce reporter mRNA levels. Using in vivo and in vitro approaches, we further document that SMG6 and the unique stalk region of the UPF1 helicase domain, along with a contribution from the SQ domain, form a novel interaction and we also show that this region of the UPF1 helicase domain is critical for SMG6 function and NMD. Our results show that this interaction is required for NMD and for the capability of tethered SMG6 to degrade its bound RNA, suggesting that it contributes to the intricate regulation of UPF1 and SMG6 enzymatic activities.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

A novel phosphorylation-independent interaction between SMG6 and UPF1 is essential for human NMD

et al. 2014

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“…The adhesion protein fibronectin (Fn) forms an interconnected network of extracellular matrix (ECM) fibres that provides structural support and many biochemical cues to cells12. The organization of the Fn matrix plays a central role for the development and regeneration of tissues by coordinating cell adhesion, growth, migration and differentiation345.…”

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confidence: 99%

Molecular architecture of native fibronectin fibrils

et al. 2015

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Fibronectin fibrils within the extracellular matrix play central roles in physiological and pathological processes, yet many structural details about their hierarchical and molecular assembly remain unknown. Here we combine site-specific protein labelling with single-molecule localization by stepwise photobleaching or direct stochastic optical reconstruction microscopy (dSTORM), and determine the relative positions of various labelled sites within native matrix fibrils. Single end-labelled fibronectin molecules in fibrils display an average end-to-end distance of ∼133 nm. Sampling of site-specific antibody epitopes along the thinnest fibrils (protofibrils) shows periodic punctate label patterns with ∼95 nm repeats and alternating N- and C-terminal regions. These measurements suggest an antiparallel 30–40 nm overlap between N-termini, suggesting that the first five type I modules bind type III modules of the adjacent molecule. Thicker fibres show random bundling of protofibrils without a well-defined line-up. This super-resolution microscopy approach can be applied to other fibrillar protein assemblies of unknown structure.

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“…All these properties of ECM might play a number of important functions for the nervous system and therefore, ECM might be involved in many physiological and pathophysiological conditions [5,7,10,36].…”

Section: Introduction the Brain Extracellular Matrix (Ecm)mentioning

confidence: 99%

“…There are three main families of core proteins: lecticans (aggrecan, brevican, neurocan and versican), phosphacan, neuro-glial antigen 2 (NG2) [11,36,43,44]. Lecticans have tree domain structure and their the N-terminal connected to hyaluronic acid via linking proteins (protein BRAL1 or HALPN2), and the C-terminal is linked to matrix proteins, such as tenascin-R or receptors on the cell surface.…”

Section: Introduction the Brain Extracellular Matrix (Ecm)mentioning

confidence: 99%

The Role of the Brain Extracellular Matrix in Synaptic Plasticity After Brain Injuries (Review)

Dembitskaya¹,

Tyurikova²,

Semyanov³

2016

Sovrem Tehnol Med

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The brain extracellular matrix is secreted by neurons and glial cells and represents a molecular net comprised of polysaccharides and proteins, fulfilling the space between cells in the tissue. A complex structure and ubiquitous localization of extracellular matrix underlie its involvement in numerous important brain functions, such as diffusion regulation, molecular cell-to-cell interactions, synaptic plasticity and learning. Additionally, the brain extracellular matrix participates in regeneration of neuronal connections after brain and spinal cord injuries. The ability to regenerate connections attenuates by the fast proliferation of the brain extracellular matrix, when its degradation leads to regeneration improvement. Therefore, the brain extracellular matrix represents an important direction of clinical research and possible target for therapeutic interventions. Here we not only describe the structure of the brain extracellular matrix and its sites of localization in the brain, but also make an overview of the influence of the brain extracellular matrix in synaptic plasticity, learning and memory. This review describes the role of the brain extracellular matrix for connection recovery after brain and spinal cord injuries. Here, we highlight the positive ability of enzymatic removal of extracellular matrix component -chondroitin sulphate proteoglycans by chondroitinase ABC to promote restoration of neuronal connections. In conclusion, we discuss possible side effects of treatments requiring the enzymatic removal of chondroitin sulphate proteoglycans on synaptic plasticity and speculate about future development of the field of the brain extracellular matrix research.

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Overview of Extracellular Matrix

Cited by 139 publications

References 94 publications

A novel phosphorylation-independent interaction between SMG6 and UPF1 is essential for human NMD

A novel phosphorylation-independent interaction between SMG6 and UPF1 is essential for human NMD

Molecular architecture of native fibronectin fibrils

The Role of the Brain Extracellular Matrix in Synaptic Plasticity After Brain Injuries (Review)

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