ArticleScientific reports2019
CLIC4 regulates late endosomal trafficking and matrix degradation activity of MMP14 at focal adhesions in RPE cells.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 18 citations in OpenAlex.
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- Chloride Intracellular Channel 2 Can Function as a Malignant Factor in Head and Neck Squamous Cell Carcinoma.Head & neck · 2026Article
- Ion channels research in hPSC-RPE cells: bridging benchwork to clinical applications.Journal of translational medicine · 2024Review
- Allele-specific expression reveals genetic drivers of tissue regeneration in mice.Cell stem cell · 2023Article
- Exosomal MicroRNA Profiling in Vitreous Humor Derived From Pathological Myopia Patients.Investigative ophthalmology & visual science · 2023Article
- Review
- The Role of Metalloproteinases and Their Tissue Inhibitors on Ocular Diseases: Focusing on Potential Mechanisms.International journal of molecular sciences · 2022Review
- Retinal pigment epithelium-specific CLIC4 mutant is a mouse model of dry age-related macular degeneration.Nature communications · 2022Article
- Chloride Channel and Inflammation-Mediated Pathogenesis of Osteoarthritis.Journal of inflammation research · 2022Review
- Chloride intracellular channel 4 (CLIC4) expression profile in the mouse medial prefrontal cortex and its regulation by ethanol.Alcoholism, clinical and experimental research · 2022Article
- Ion channels as a therapeutic target for renal fibrosis.Frontiers in physiology · 2022Review
- Matrix Metalloproteinases Shape the Tumor Microenvironment in Cancer Progression.International journal of molecular sciences · 2021Review
- A Literature-Derived Knowledge Graph Augments the Interpretation of Single Cell RNA-seq Datasets.Genes · 2021Article
- Article
- Establishment of an Endocytosis-Related Prognostic Signature for Patients With Low-Grade Glioma.Frontiers in genetics · 2021Article
- How Dysregulated Ion Channels and Transporters Take a Hand in Esophageal, Liver, and Colorectal Cancer.Reviews of physiology, biochemistry and pharmacology · 2021Review
- Hold on or Cut? Integrin- and MMP-Mediated Cell-Matrix Interactions in the Tumor Microenvironment.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 2 countries.
Funding
Abstract
Dysregulation in the extracellular matrix (ECM) microenvironment surrounding the retinal pigment epithelium (RPE) has been implicated in the etiology of proliferative vitreoretinopathy and age-related macular degeneration. The regulation of ECM remodeling by RPE cells is not well understood. We show that membrane-type matrix metalloproteinase 14 (MMP14) is central to ECM degradation at the focal adhesions in human ARPE19 cells. The matrix degradative activity, but not the assembly, of the focal adhesion is regulated by chloride intracellular channel 4 (CLIC4). CLIC4 is co-localized with MMP14 in the late endosome. CLIC4 regulates the proper sorting of MMP14 into the lumen of the late endosome and its proteolytic activation in lipid rafts. CLIC4 has the newly-identified "late domain" motif that binds to MMP14 and to Tsg101, a component of the endosomal sorting complex required for transport (ESCRT) complex. Unlike the late domain mutant CLIC4, wild-type CLIC4 can rescue the late endosomal sorting defect of MMP14. Finally, CLIC4 knockdown inhibits the apical secretion of MMP2 in polarized human RPE monolayers. These results, taken together, demonstrate that CLIC4 is a novel matrix microenvironment modulator and a novel regulator for late endosomal cargo sorting. Moreover, the late endosomal sorting of MMP14 actively regulates its surface activation in RPE cells.
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Registered trials
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