ArticleCardiovascular research2013
Cardiomyocyte ryanodine receptor degradation by chaperone-mediated autophagy.
Article in Cardiovascular research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 64 citations in OpenAlex.
- Recycle, repair, recover: the role of autophagy in modulating skeletal muscle repair and post-exercise recovery.Bioscience reports · 2025Review
- HSPA8 Activates Wnt/β-Catenin Signaling to Facilitate BRAF V600E Colorectal Cancer Progression by CMA-Mediated CAV1 Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Autophagy and regulation of aquaporins in the kidneys.Kidney research and clinical practice · 2023Article
- Autophagy, innate immunity, and cardiac disease.Frontiers in cell and developmental biology · 2023Review
- Chaperone-mediated autophagy protects cardiomyocytes against hypoxic-cell death.American journal of physiology. Cell physiology · 2022Article
- Review
- Review
- The role of autophagy in cardiovascular pathology.Cardiovascular research · 2022Review
- Synergistic stimulation of osteoblast differentiation of rat mesenchymal stem cells by leptin and 25(OH)DStem cell research & therapy · 2021Article
- Desmin aggrephagy in rat and human ischemic heart failure through PKCζ and GSK3β as upstream signaling pathways.Cell death discovery · 2021Article
- Dysfunction of chaperone-mediated autophagy in human diseases.Molecular and cellular biochemistry · 2021Review
- Sodium channel β1 subunits participate in regulated intramembrane proteolysis-excitation coupling.JCI insight · 2021Article
- Calcium Ions Aggravate Alzheimer's Disease Through the Aberrant Activation of Neuronal Networks, Leading to Synaptic and Cognitive Deficits.Frontiers in molecular neuroscience · 2021Review
- Impact of Chaperone-Mediated Autophagy in Brain Aging: Neurodegenerative Diseases and Glioblastoma.Frontiers in aging neuroscience · 2020Article
- Berberine Promotes Cardiac Function by Upregulating PINK1/Parkin-Mediated Mitophagy in Heart Failure.Frontiers in physiology · 2020Article
- Resolving the topological enigma in CaThe Journal of biological chemistry · 2019Review
- Neferine induces autophagy-dependent cell death in apoptosis-resistant cancers via ryanodine receptor and CaScientific reports · 2019Article
- A cytosolic chaperone complex controls folding and degradation of type III CD38.The Journal of biological chemistry · 2019Article
- Genome-wide association study of myocardial infarction, atrial fibrillation, acute stroke, acute kidney injury and delirium after cardiac surgery - a sub-analysis of the RIPHeart-Study.BMC cardiovascular disorders · 2019Article
- The coming of age of chaperone-mediated autophagy.Nature reviews. Molecular cell biology · 2018Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
aimsChaperone-mediated autophagy (CMA) is a selective mechanism for the degradation of soluble cytosolic proteins bearing the sequence KFERQ. These proteins are targeted by chaperones and delivered to lysosomes where they are translocated into the lysosomal lumen and degraded via the lysosome-associated membrane protein type 2A (LAMP-2A). Mutations in LAMP2 that inhibit autophagy result in Danon disease characterized by hypertrophic cardiomyopathy. The ryanodine receptor type 2 (RyR2) plays a key role in cardiomyocyte excitation-contraction and its dysfunction can lead to cardiac failure. Whether RyR2 is degraded by CMA is unknown. METHODS AND
resultsTo induce CMA, cultured neonatal rat cardiomyocytes were treated with geldanamycin (GA) to promote protein degradation through this pathway. GA increased LAMP-2A levels together with its redistribution and colocalization with Hsc70 in the perinuclear region, changes indicative of CMA activation. The inhibition of lysosomes but not proteasomes prevented the loss of RyR2. The recovery of RyR2 content after incubation with GA by siRNA targeting LAMP-2A suggests that RyR2 is degraded via CMA. In silico analysis also revealed that the RyR2 sequence harbours six KFERQ motifs which are required for the recognition Hsc70 and its degradation via CMA. Our data suggest that presenilins are involved in RyR2 degradation by CMA.
conclusionThese findings are consistent with a model in which oxidative damage of the RyR2 targets it for turnover by presenilins and CMA, which could lead to removal of damaged or leaky RyR2 channels.
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Registered trials
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.