Form and function of the apical extracellular matrix: new insights from Caenorhabditis elegans, Drosophila melanogaster, and the vertebrate inner ear

Zheng, Sherry Li; Adams, Jennifer Gotenstein; Chisholm, Andrew

doi:10.12703/r/9-27

Cited by 26 publications

(17 citation statements)

References 71 publications

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“…This gene is also important for ER processing of cuticle collagen cargos and apical ECM (aECM) formation in Drosophila melanogaster. These findings highlight the conserved role of this gene in collogen biosynthesis ( 74 ). The methylation rate of this gene is reduced in T-Cells and peripheral blood cells in Down syndrome patients (Trisomy 21).…”

Section: Discussionsupporting

confidence: 53%

Systems Biomedicine of Primary and Metastatic Colorectal Cancer Reveals Potential Therapeutic Targets

et al. 2021

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Colorectal cancer (CRC) is one of the major causes of cancer deaths across the world. Patients’ survival at time of diagnosis depends mainly on stage of the tumor. Therefore, understanding the molecular mechanisms from low-grade to high-grade stages of cancer that lead to cellular migration from one tissue/organ to another tissue/organ is essential for implementing therapeutic approaches. To this end, we performed a unique meta-analysis flowchart by identifying differentially expressed genes (DEGs) between normal, primary (primary sites), and metastatic samples (Colorectal metastatic lesions in liver and lung) in some Test datasets. DEGs were employed to construct a protein-protein interaction (PPI) network. A smaller network containing 39 DEGs was then extracted from the PPI network whose nodes expression induction or suppression alone or in combination with each other would inhibit tumor progression or metastasis. These DEGs were then verified by gene expression profiling, survival analysis, and multiple Validation datasets. We suggested for the first time that downregulation of mitochondrial genes, including ETHE1, SQOR, TST, and GPX3, would help colorectal cancer cells to produce more energy under hypoxic conditions through mechanisms that are different from “Warburg Effect”. Augmentation of given antioxidants and repression of P4HA1 and COL1A2 genes could be a choice of CRC treatment. Moreover, promoting active GSK-3β together with expression control of EIF2B would prevent EMT. We also proposed that OAS1 expression enhancement can induce the anti-cancer effects of interferon-gamma, while suppression of CTSH hinders formation of focal adhesions. ATF5 expression suppression sensitizes cancer cells to anchorage-dependent death signals, while LGALS4 induction recovers cell-cell junctions. These inhibitions and inductions would be another combinatory mechanism that inhibits EMT and cell migration. Furthermore, expression inhibition of TMPO, TOP2A, RFC3, GINS1, and CKS2 genes could prevent tumor growth. Besides, TRIB3 suppression would be a promising target for anti−angiogenic therapy. SORD is a poorly studied enzyme in cancer, found to be upregulated in CRC. Finally, TMEM131 and DARS genes were identified in this study whose roles have never been interrogated in any kind of cancer, neither as a biomarker nor curative target. All the mentioned mechanisms must be further validated by experimental wet-lab techniques.

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Section: Discussionsupporting

confidence: 53%

Systems Biomedicine of Primary and Metastatic Colorectal Cancer Reveals Potential Therapeutic Targets

et al. 2021

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“…Specialized extracellular matrices cover the apical surface of all epithelial cells and form the skin in almost all animals (Li Zheng et al, 2020). These apical extracellular matrices (aECMs) also line the lumen of internal tubular epithelia to form a protective layer against biotic and abiotic threats (Li Zheng et al, 2020). Despite their importance, understanding the structure and dynamics of aECM components in development and disease remains challenging.…”

Section: Introductionmentioning

confidence: 99%

The conserved, secreted protease inhibitor MLT-11 is necessary for C. elegans molting and embryogenesis

Ragle

Levenson

Clancy

et al. 2022

Preprint

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Apical extracellular matrices (aECMs) are associated with all epithelia and form a protective layer against biotic and abiotic threats in the environment. C. elegans molting offers a powerful entry point to understanding developmentally programmed aECM remodeling. Several protease inhibitors are implicated in molting, but their functions remain poorly understood. Here we characterize mlt-11, an unusual protease inhibitor with 10 conserved Kunitz domains. MLT-11 oscillates and is localized in the cuticle and in lysosomes in larvae and in the embryonic sheath starting at the 3-fold embryo stage. mlt-11 (RNAi) produced a developmental delay, motility defects, failed apolysis, and a defective cuticle barrier. mlt-11 null and C-terminal Kunitz domain deletion mutants are embryonic lethal while N-terminal deletions cause a rolling phenotype indicative of cuticle structure abnormalities. mlt-11 activity is primarily necessary in seam and hypodermal cells and accordingly mlt-11 (RNAi) causes defects in localization of the collagens ROL-6 and BLI-1 over the cuticle. mlt-11 (RNAi) molting phenotypes can be suppressed by genetically inhibiting endocytosis. Our model is that MLT-11 is acting in the aECM to coordinate remodeling and timely ecdysis.

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“…This time period coincides with tendon cell elongation and morphological changes occurring within developing muscles that are also being subjected to increased resistive tension. Arrays of F-actin fibers overlapping with specialized microtubules with 15 tubulin protofilaments and myosin II have been reported in the cytosol of wing cells and in tendon cells of D. melanogaster ( 12 , 46 , 47 ). It has been proposed that these microtubule arrays play a critical role in stiffening tendon cells presumably assisted by cross-linking or stabilization of microtubules mediated by proteins, such as Shortstop/Spectraplakin and the microtubule minus-end binding protein, Patronin ( 48 , 49 ).…”

Section: Discussionmentioning

confidence: 99%

Chitin deacetylases are necessary for insect femur muscle attachment and mobility

Mun

Noh

Geisbrecht

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Muscle attachment sites (MASs, apodemes) in insects and other arthropods involve specialized epithelial cells, called tendon cells or tenocytes, that adhere to apical extracellular matrices containing chitin. Here, we have uncovered a function for chitin deacetylases (CDAs) in arthropod locomotion and muscle attachment using a double-stranded RNA-mediated gene-silencing approach targeted toward specific CDA isoforms in the red flour beetle, Tribolium castaneum ( Tc ). Depletion of TcCDA1 or the alternatively spliced TcCDA2 isoform, TcCDA2a, resulted in internal tendon cuticle breakage at the femur–tibia joint, muscle detachment from both internal and external tendon cells, and defective locomotion. TcCDA deficiency did not affect early muscle development and myofiber growth toward the cuticular MASs but instead resulted in aborted microtubule development, loss of hemiadherens junctions, and abnormal morphology of tendon cells, all features consistent with a loss of tension within and between cells. Moreover, simultaneous depletion of TcCDA1 or TcCDA2a and the zona pellucida domain protein, TcDumpy, prevented the internal tendon cuticle break, further supporting a role for force-dependent interactions between muscle and tendon cells. We propose that in T. castaneum , the absence of N -acetylglucosamine deacetylation within chitin leads to a loss of microtubule organization and reduced membrane contacts at MASs in the femur, which adversely affect musculoskeletal connectivity, force transmission, and physical mobility.

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Form and function of the apical extracellular matrix: new insights from Caenorhabditis elegans, Drosophila melanogaster, and the vertebrate inner ear

Cited by 26 publications

References 71 publications

Systems Biomedicine of Primary and Metastatic Colorectal Cancer Reveals Potential Therapeutic Targets

Systems Biomedicine of Primary and Metastatic Colorectal Cancer Reveals Potential Therapeutic Targets

The conserved, secreted protease inhibitor MLT-11 is necessary for C. elegans molting and embryogenesis

Chitin deacetylases are necessary for insect femur muscle attachment and mobility

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