ArticleBMC cell biology2010
Regulation of endocytic trafficking of transferrin receptor by optineurin and its impairment by a glaucoma-associated mutant.
Article in BMC cell biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 104 citations in OpenAlex.
- Differentially expressed microRNAs in the aqueous humor of patients with exfoliation glaucoma or primary open-angle glaucoma.Human molecular genetics · 2018Trial
- Ferroptosis and retinal ganglion cell death in glaucoma: Mechanisms and therapeutic approaches.Journal of pharmaceutical analysis · 2026Review
- OPTN protects retinal ganglion cells and ameliorates neuroinflammation in optic neuropathies.Communications biology · 2025Article
- Age-related effects of optineurin deficiency in the mouse eye.Vision research · 2024Article
- Conversion of Optineurin into an Hsp72-Inducible protein by C-terminal addition of green fluorescent protein.Molecular vision · 2024Article
- Emerging views of OPTN (optineurin) function in the autophagic process associated with disease.Autophagy · 2022Review
- OPTN recruitment to a Golgi-proximal compartment regulates immune signalling and cytokine secretion.Journal of cell science · 2020Article
- The Genetic and Endoplasmic Reticulum-Mediated Molecular Mechanisms of Primary Open-Angle Glaucoma.International journal of molecular sciences · 2020Review
- Disrupted neuronal trafficking in amyotrophic lateral sclerosis.Acta neuropathologica · 2019Review
- Article
- Optineurin downregulation induces endoplasmic reticulum stress, chaperone-mediated autophagy, and apoptosis in pancreatic cancer cells.Cell death discovery · 2019Article
- Research progress on human genes involved in the pathogenesis of glaucoma (Review).Molecular medicine reports · 2018Review
- LRRK2 mediated Rab8a phosphorylation promotes lipid storage.Lipids in health and disease · 2018Article
- Optineurin promotes autophagosome formation by recruiting the autophagy-related Atg12-5-16L1 complex to phagophores containing the Wipi2 protein.The Journal of biological chemistry · 2018Article
- Optineurin: A Coordinator of Membrane-Associated Cargo Trafficking and Autophagy.Frontiers in immunology · 2018Review
- Dysfunction of Optineurin in Amyotrophic Lateral Sclerosis and Glaucoma.Frontiers in immunology · 2018Review
- Altered Functions and Interactions of Glaucoma-Associated Mutants of Optineurin.Frontiers in immunology · 2018Review
- Structural insights into the ubiquitin recognition by OPTN (optineurin) and its regulation by TBK1-mediated phosphorylation.Autophagy · 2018Article
- Yeast genetic interaction screen of human genes associated with amyotrophic lateral sclerosis: identification of MAP2K5 kinase as a potential drug target.Genome research · 2017Article
- Major review: Molecular genetics of primary open-angle glaucoma.Experimental eye research · 2017Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOptineurin is a multifunctional protein involved in several functions such as vesicular trafficking from the Golgi to the plasma membrane, NF-kappaB regulation, signal transduction and gene expression. Mutations in optineurin are associated with glaucoma, a neurodegenerative eye disease that causes blindness. Genetic evidence suggests that the E50K (Glu50Lys) is a dominant disease-causing mutation of optineurin. However, functional alterations caused by mutations in optineurin are not known. Here, we have analyzed the role of optineurin in endocytic recycling and the effect of E50K mutant on this process.
resultsWe show that the knockdown of optineurin impairs trafficking of transferrin receptor to the juxtanuclear region. A point mutation (D474N) in the ubiquitin-binding domain abrogates localization of optineurin to the recycling endosomes and interaction with transferrin receptor. The function of ubiquitin-binding domain of optineurin is also needed for trafficking of transferrin to the juxtanuclear region. A disease causing mutation, E50K, impairs endocytic recycling of transferrin receptor as shown by enlarged recycling endosomes, slower dynamics of E50K vesicles and decreased transferrin uptake by the E50K-expressing cells. This impaired trafficking by the E50K mutant requires the function of its ubiquitin-binding domain. Compared to wild type optineurin, the E50K optineurin shows enhanced interaction and colocalization with transferrin receptor and Rab8. The velocity of Rab8 vesicles is reduced by co-expression of the E50K mutant. These results suggest that the E50K mutant affects Rab8-mediated transferrin receptor trafficking.
conclusionsOur results suggest that optineurin regulates endocytic trafficking of transferrin receptor to the juxtanuclear region. The E50K mutant impairs trafficking at the recycling endosomes due to altered interactions with Rab8 and transferrin receptor. These results also have implications for the pathogenesis of glaucoma caused by the E50K mutation because endocytic recycling is vital for maintaining homeostasis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.