دورية أكاديمية
أعرض في EDS

Autophagy is inhibited by ubiquitin ligase activity in the nervous system.

التفاصيل البيبلوغرافية
العنوان: Autophagy is inhibited by ubiquitin ligase activity in the nervous system.
المؤلفون: Crawley O; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL, 33458, USA., Opperman KJ; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL, 33458, USA., Desbois M; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL, 33458, USA., Adrados I; Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL, 33458, USA., Borgen MA; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL, 33458, USA., Giles AC; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL, 33458, USA., Duckett DR; Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL, 33458, USA.; Department of Drug Discovery, Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA., Grill B; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL, 33458, USA. bgrill@scripps.edu.
المصدر: Nature communications [Nat Commun] 2019 Nov 01; Vol. 10 (1), pp. 5017. Date of Electronic Publication: 2019 Nov 01.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Autophagy/*physiology , Caenorhabditis elegans/*metabolism , Caenorhabditis elegans Proteins/*metabolism , Guanine Nucleotide Exchange Factors/*metabolism , Neurodegenerative Diseases/*metabolism , Neurons/*metabolism , Ubiquitin-Protein Ligases/*metabolism, Animals ; Animals, Genetically Modified ; Autophagosomes/metabolism ; Autophagy/genetics ; Autophagy-Related Protein-1 Homolog/genetics ; Autophagy-Related Protein-1 Homolog/metabolism ; Axons/metabolism ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans Proteins/genetics ; Cell Line, Tumor ; Guanine Nucleotide Exchange Factors/genetics ; HEK293 Cells ; Humans ; Neurodegenerative Diseases/genetics ; Protein Serine-Threonine Kinases/genetics ; Protein Serine-Threonine Kinases/metabolism ; Proteomics/methods ; Synapses/genetics ; Synapses/metabolism ; Ubiquitin-Protein Ligases/genetics
مستخلص: Autophagy is an intracellular catabolic process prominent in starvation, aging and disease. Neuronal autophagy is particularly important, as it affects the development and function of the nervous system, and is heavily implicated in neurodegenerative disease. Nonetheless, how autophagy is regulated in neurons remains poorly understood. Using an unbiased proteomics approach, we demonstrate that the primary initiator of autophagy, the UNC-51/ULK kinase, is negatively regulated by the ubiquitin ligase RPM-1. RPM-1 ubiquitin ligase activity restricts UNC-51 and autophagosome formation within specific axonal compartments, and exerts effects broadly across the nervous system. By restraining UNC-51 activity, RPM-1 inhibits autophagosome formation to affect axon termination, synapse maintenance and behavioral habituation. These results demonstrate how UNC-51 and autophagy are regulated subcellularly in axons, and unveils a mechanism for restricting initiation of autophagy across the nervous system. Our findings have important implications beyond nervous system development, given growing links between altered autophagy regulation and neurodegenerative diseases.
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معلومات مُعتمدة: R01 NS072129 United States NS NINDS NIH HHS
المشرفين على المادة: 0 (Caenorhabditis elegans Proteins)
0 (Guanine Nucleotide Exchange Factors)
0 (RPM-1 protein, C elegans)
EC 2.3.2.27 (Ubiquitin-Protein Ligases)
EC 2.7.1.- (UNC-51 protein, C elegans)
EC 2.7.11.1 (Autophagy-Related Protein-1 Homolog)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)
تواريخ الأحداث: Date Created: 20191103 Date Completed: 20200316 Latest Revision: 20211204
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC6825199
DOI: 10.1038/s41467-019-12804-3
PMID: 31676756
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-019-12804-3