ArticleeLife2017
Multiplex image-based autophagy RNAi screening identifies SMCR8 as ULK1 kinase activity and gene expression regulator.
Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 76 citations in OpenAlex.
- Poly-GP accumulation due to C9orf72 loss of function induces motor neuron apoptosis through autophagy and mitophagy defects.Autophagy · 2024Article
- Aberrant protein aggregation in amyotrophic lateral sclerosis.Journal of neurology · 2024Review
- Cdk5 phosphorylation-dependent C9orf72 degradation promotes neuronal death in Parkinson's disease models.CNS neuroscience & therapeutics · 2023Article
- Article
- Non-muscle MYH10/myosin IIB recruits ESCRT-III to participate in autophagosome closure to maintain neuronal homeostasis.Autophagy · 2023Article
- C9ORF72 knockdown triggers FTD-like symptoms and cell pathology in mice.Frontiers in cellular neuroscience · 2023Article
- Autophagy and neurodegeneration: Unraveling the role of C9ORF72 in the regulation of autophagy and its relationship to ALS-FTD pathology.Frontiers in cellular neuroscience · 2023Review
- Multi-omics profiling identifies a deregulated FUS-MAP1B axis in ALS/FTD-associated UBQLN2 mutants.Life science alliance · 2022Article
- Autophagy and beyond: Unraveling the complexity of UNC-51-like kinase 1 (ULK1) from biological functions to therapeutic implications.Acta pharmaceutica Sinica. B · 2022Review
- Review
- The progress inSmall GTPases · 2022Review
- C9orf72 ALS-FTD: recent evidence for dysregulation of the autophagy-lysosome pathway at multiple levels.Autophagy · 2021Review
- Structure of the human C9orf72-SMCR8 complex reveals a multivalent protein interaction architecture.PLoS biology · 2021Article
- Lysosome dysfunction as a cause of neurodegenerative diseases: Lessons from frontotemporal dementia and amyotrophic lateral sclerosis.Neurobiology of disease · 2021Review
- The Cryo-EM Effect: Structural Biology of Neurodegenerative Disease Proteostasis Factors.Journal of neuropathology and experimental neurology · 2021Review
- Cellular and physiological functions of C9ORF72 and implications for ALS/FTD.Journal of neurochemistry · 2021Review
- Golgi-associated Rab GTPases implicated in autophagy.Cell & bioscience · 2021Review
- Mitochondrial Fission Protein 1: Emerging Roles in Organellar Form and Function in Health and Disease.Frontiers in endocrinology · 2021Review
- Zmat3 Is a Key Splicing Regulator in the p53 Tumor Suppression Program.Molecular cell · 2020Article
- RNA-mediated toxicity in C9orf72 ALS and FTD.Neurobiology of disease · 2020Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy is an intracellular recycling and degradation pathway that depends on membrane trafficking. Rab GTPases are central for autophagy but their regulation especially through the activity of Rab GEFs remains largely elusive. We employed a RNAi screen simultaneously monitoring different populations of autophagosomes and identified 34 out of 186 Rab GTPase, GAP and GEF family members as potential autophagy regulators, amongst them SMCR8. SMCR8 uses overlapping binding regions to associate with C9ORF72 or with a C9ORF72-ULK1 kinase complex holo-assembly, which function in maturation and formation of autophagosomes, respectively. While focusing on the role of SMCR8 during autophagy initiation, we found that kinase activity and gene expression of ULK1 are increased upon SMCR8 depletion. The latter phenotype involved association of SMCR8 with the ULK1 gene locus. Global mRNA expression analysis revealed that SMCR8 regulates transcription of several other autophagy genes including WIPI2. Collectively, we established SMCR8 as multifaceted negative autophagy regulator.
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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.