Altered Functions and Interactions of Glaucoma-Associated Mutants of Optineurin
| Autor: | Zuberwasim Sayyad, Ghanshyam Swarup |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Retinal Ganglion Cells
lcsh:Immunologic diseases. Allergy 0301 basic medicine autophagy Programmed cell death TBK1 CYLD Immunology Autoimmunity Cell Cycle Proteins Review Biology Retinal ganglion NF-κB 03 medical and health sciences 0302 clinical medicine TANK-binding kinase 1 Transcription Factor TFIIIA Rab8 Animals Humans Immunology and Allergy Genetic Predisposition to Disease Protein kinase A Transcription factor Alleles Genetic Association Studies Optineurin Amyotrophic Lateral Sclerosis Autophagy NF-kappa B Membrane Transport Proteins Signal transducing adaptor protein optineurin Cell biology Disease Models Animal Protein Transport glaucoma 030104 developmental biology Mutation vesicle trafficking 030221 ophthalmology & optometry lcsh:RC581-607 Signal Transduction |
| Zdroj: | Frontiers in Immunology, Vol 9 (2018) Frontiers in Immunology |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2018.01287 |
| Popis: | Optineurin (OPTN) is an adaptor protein that is involved in mediating a variety of cellular processes such as signaling, vesicle trafficking, and autophagy. Certain mutations in OPTN (gene OPTN) are associated with primary open angle glaucoma, a leading cause of irreversible blindness, and amyotrophic lateral sclerosis, a fatal motor neuron disease. Glaucoma-associated mutations of OPTN are mostly missense mutations. OPTN mediates its functions by interacting with various proteins and altered interactions of OPTN mutants with various proteins primarily contribute to functional defects. It interacts with Rab8, myosin VI, Huntigtin, TBC1D17, and transferrin receptor to mediate various membrane vesicle trafficking pathways. It is an autophagy receptor that mediates cargo-selective as well as non-selective autophagy. Glaucoma-associated mutants of OPTN, E50K, and M98K, cause defective vesicle trafficking, autophagy, and signaling that contribute to death of retinal ganglion cells (RGCs). Transgenic mice expressing E50K-OPTN show loss of RGCs and persistent reactive gliosis. TBK1 protein kinase, which mediates E50K-OPTN and M98K-OPTN induced cell death, is emerging as a potential drug target. Autoimmunity has been implicated in glaucoma but involvement of OPTN or its mutants in autoimmnity has not been explored. In this review, we highlight the main functions of OPTN and how glaucoma-associated mutants alter these functions. We also discuss some of the controversies, such as the role of OPTN in signaling to transcription factor NF-κB, interferon signaling, and use of RGC-5 cell line as a cell culture model. |
| Databáze: | OpenAIRE |
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