دورية أكاديمية
Homeostatic scaling is driven by a translation-dependent degradation axis that recruits miRISC remodeling.
العنوان: | Homeostatic scaling is driven by a translation-dependent degradation axis that recruits miRISC remodeling. |
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المؤلفون: | Srinivasan B; National Brain Research Centre, Manesar, India., Samaddar S; National Brain Research Centre, Manesar, India., Mylavarapu SVS; Regional Centre for Biotechnology, Faridabad, India., Clement JP; Neuroscience Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru, India., Banerjee S; National Brain Research Centre, Manesar, India. |
المصدر: | PLoS biology [PLoS Biol] 2021 Nov 23; Vol. 19 (11), pp. e3001432. Date of Electronic Publication: 2021 Nov 23 (Print Publication: 2021). |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101183755 Publication Model: eCollection Cited Medium: Internet ISSN: 1545-7885 (Electronic) Linking ISSN: 15449173 NLM ISO Abbreviation: PLoS Biol Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: San Francisco, CA : Public Library of Science, [2003]- |
مواضيع طبية MeSH: | Proteolysis*, Homeostasis/*genetics , MicroRNAs/*metabolism , Protein Biosynthesis/*genetics , RNA-Induced Silencing Complex/*metabolism, Animals ; Cytoskeletal Proteins/metabolism ; Mechanistic Target of Rapamycin Complex 1/metabolism ; MicroRNAs/genetics ; Nerve Tissue Proteins/metabolism ; Neurons/metabolism ; Phosphorylation ; Polyribosomes/metabolism ; Polyubiquitin/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Rats, Sprague-Dawley ; Receptors, AMPA/metabolism ; Ribosomal Protein S6 Kinases, 70-kDa/metabolism ; Synapses/metabolism ; Transcription Factors/metabolism ; Tripartite Motif Proteins/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination ; Rats |
مستخلص: | Homeostatic scaling in neurons has been attributed to the individual contribution of either translation or degradation; however, there remains limited insight toward understanding how the interplay between the two processes effectuates synaptic homeostasis. Here, we report that a codependence between protein synthesis and degradation mechanisms drives synaptic homeostasis, whereas abrogation of either prevents it. Coordination between the two processes is achieved through the formation of a tripartite complex between translation regulators, the 26S proteasome, and the miRNA-induced silencing complex (miRISC) components such as Argonaute, MOV10, and Trim32 on actively translating transcripts or polysomes. The components of this ternary complex directly interact with each other in an RNA-dependent manner. Disruption of polysomes abolishes this ternary interaction, suggesting that translating RNAs facilitate the combinatorial action of the proteasome and the translational apparatus. We identify that synaptic downscaling involves miRISC remodeling, which entails the mTORC1-dependent translation of Trim32, an E3 ligase, and the subsequent degradation of its target, MOV10 via the phosphorylation of p70 S6 kinase. We find that the E3 ligase Trim32 specifically polyubiquitinates MOV10 for its degradation during synaptic downscaling. MOV10 degradation alone is sufficient to invoke downscaling by enhancing Arc translation through its 3' UTR and causing the subsequent removal of postsynaptic AMPA receptors. Synaptic scaling was occluded when we depleted Trim32 and overexpressed MOV10 in neurons, suggesting that the Trim32-MOV10 axis is necessary for synaptic downscaling. We propose a mechanism that exploits a translation-driven protein degradation paradigm to invoke miRISC remodeling and induce homeostatic scaling during chronic network activity. Competing Interests: The authors have declared that no competing interests exist. |
التعليقات: | Comment in: PLoS Biol. 2021 Nov 24;19(11):e3001448. (PMID: 34818347) |
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المشرفين على المادة: | 0 (Cytoskeletal Proteins) 0 (MicroRNAs) 0 (Nerve Tissue Proteins) 0 (RNA-Induced Silencing Complex) 0 (Receptors, AMPA) 0 (Transcription Factors) 0 (Tripartite Motif Proteins) 0 (activity regulated cytoskeletal-associated protein) 120904-94-1 (Polyubiquitin) EC 2.3.2.27 (Ubiquitin-Protein Ligases) EC 2.3.2.27 (trim32 protein, rat) EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1) EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa) EC 3.4.25.1 (Proteasome Endopeptidase Complex) |
تواريخ الأحداث: | Date Created: 20211123 Date Completed: 20211221 Latest Revision: 20240226 |
رمز التحديث: | 20240226 |
مُعرف محوري في PubMed: | PMC8610276 |
DOI: | 10.1371/journal.pbio.3001432 |
PMID: | 34813590 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1545-7885 |
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DOI: | 10.1371/journal.pbio.3001432 |