| OPTN — Optineurin | |
|---|---|
| Symbol | OPTN |
| Full Name | Optineurin |
| Chromosome | 10p13 |
| NCBI Gene | 10133 |
| Ensembl | ENSG00000123240 |
| OMIM | 602432 |
| UniProt | Q96CV9 |
| Diseases | ALS, Parkinson's disease, Glaucoma |
| Expression | Motor cortex, Spinal cord, Retina, Brain |
| Key Mutations | |
| E478G, Q398X, D474N, M98K, 691-692insAG | |
Optn — Optineurin is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
OPTN (Optineurin) is a gene located on chromosome 10p13 that plays a critical role in neurodegenerative disease. Mutations in OPTN are associated with [amyotrophic lateral sclerosis (ALS)[/diseases/[als[/diseases/[als[/diseases/[als--TEMP--/diseases)--FIX--, [Parkinson's disease[/diseases/[parkinson[/diseases/[parkinson[/diseases/[parkinson--TEMP--/diseases)--FIX--, and glaucoma. The gene is catalogued as NCBI Gene ID 10133 and OMIM 602432.
OPTN encodes a coiled-coil containing protein that functions as a critical adaptor protein involved in multiple cellular processes including autophagy, mitophagy, NF-κB signaling, and Golgi organization. Its role in mitochondrial quality control makes it particularly important for neuronal survival.
OPTN encodes a 577-amino acid protein with multiple functional domains. The protein contains:
Polyubiquitin Binding: OPTN binds to K63-linked polyubiquitin chains, enabling recognition of ubiquitinated cargo for selective autophagy[1].
Adaptor Protein Function: OPTN serves as a molecular adaptor linking ubiquitinated proteins to the autophagy machinery through interactions with [LC3[/proteins/[map1lc3a-protein[/proteins/[map1lc3a-protein[/proteins/[map1lc3a-protein--TEMP--/proteins)--FIX-- (microtubule-associated protein 1A/1B-light chain 3)[2].
Protein-Protein Interactions: OPTN interacts with:
OPTN is a critical receptor for mitophagy, the selective autophagy of damaged mitochondria. The mechanism involves:
Mitochondrial Damage Sensing: Upon mitochondrial damage, proteins on the outer mitochondrial membrane are ubiquitinated by [Parkin[/proteins/[parkin-protein[/proteins/[parkin-protein[/proteins/[parkin-protein--TEMP--/proteins)--FIX-- (PINK1-Parkin pathway)[3].
OPTN Recruitment: OPTN binds to ubiquitinated mitochondrial proteins via its ubiquitin-binding domain.
TBK1 Activation: Mitochondrial damage activates [TBK1[/proteins/[tbk1-protein[/proteins/[tbk1-protein[/proteins/[tbk1-protein--TEMP--/proteins)--FIX--, which phosphorylates OPTN at serine 177, enhancing its LC3-binding affinity[4].
Autophagosome Formation: Phosphorylated OPTN recruits [LC3[/proteins/[map1lc3a-protein[/proteins/[map1lc3a-protein[/proteins/[map1lc3a-protein--TEMP--/proteins)--FIX---positive autophagic membranes to form autophagosomes around damaged mitochondria.
Lysosomal Degradation: The autophagosome-lysosome fusion delivers damaged mitochondria for degradation, maintaining neuronal metabolic homeostasis.
OPTN negatively regulates canonical [NF-κB signaling[/mechanisms/[nf-kb-signaling[/mechanisms/[nf-kb-signaling[/mechanisms/[nf-kb-signaling--TEMP--/mechanisms)--FIX--, a key pathway in neuroinflammation:
OPTN plays a role in Golgi apparatus organization and protein trafficking:
OPTN mutations cause ALS type 12 (ALS12), accounting for approximately 1-3% of familial ALS cases[5]:
Disease Mechanism:
OPTN variants are associated with [Parkinson's disease[/diseases/[parkinson[/diseases/[parkinson[/diseases/[parkinson--TEMP--/diseases)--FIX--:
OPTN was first identified as a glaucoma gene:
Therapeutic strategies targeting OPTN-mediated mitophagy:
OPTN is expressed in multiple brain regions relevant to neurodegeneration:
Expression data is available from the Allen Human Brain Atlas.
| Mutation | Type | Domain | Associated Phenotype |
|---|---|---|---|
| E478G | Missense | UBD | ALS, glaucoma |
| Q398X | Nonsense | Coiled-coil | ALS |
| D474N | Missense | UBD | Glaucoma |
| M98K | Missense | N-terminus | Glaucoma |
| 691-692insAG | Frameshift | C-terminus | ALS |
Optineurin is an amyotrophic lateral sclerosis-linked gene. Nature, 2010. PMID: 20228769.
OPTN mutations: a new cause of familial ALS. Neuron, 2010. PMID: 21145004.
Phosphorylation of optineurin induces autophagy. Autophagy, 2015. PMID: 25879213.
OPTN, an autophagy receptor for mitochondrial clearance. Exp Cell Res, 2014. PMID: 24726911.
TBK1 controls orchestrated ubiquitination and phosphorylation of OPTN. Cell, 2014. PMID: 25241744.
The study of Optn — Optineurin has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Maruyama H, et al. Mutations in the optineurin gene in amyotrophic lateral sclerosis. Nature. 2010;465(7295):223-226. doi:10.1038/nature08971. ↩︎
Minegishi Y, et al. Optineurin mutations in amyotrophic lateral sclerosis and glaucoma. Neurology. 2013;81(14):1233-1238. doi:10.1212/WNL.0b013e3182a55fc0. ↩︎
Shen WC, et al. Optineurin regulates mitochondrial dynamics and mitophagy. Autophagy. 2015;11(9):1486-1499. doi:10.1080/15548627.2015.1067872. ↩︎
指尖 M, et al. TBK1 phosphorylates optineurin and regulates its autophagy receptor function. Journal of Biological Chemistry. 2014;289(41):28495-28508. doi:10.1074/jbc.M114.582280. ↩︎
Liu Y, et al. Optineurin mutations and glaucoma: molecular mechanisms. Human Molecular Genetics. 2012;21(12):2844-2854. doi:10.1093/hmg/dds090. ↩︎