New emerging roles of Polycystin-2 in the regulation of autophagy

Peña‐Oyarzún, Daniel; Batista‐González, Ana; Kretschmar, Catalina; Burgos, Paulina; Lavandero, Sergio; Morselli, Eugenia; Criollo, Alfredo

doi:10.1016/bs.ircmb.2020.02.006

Cited by 8 publications

(5 citation statements)

References 107 publications

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“…Autosomal‐dominant polycystic kidney disease (ADPKD) is the most common genetic form of chronic renal disease. The appearance of the pathological phenotype is causally linked to mutations in the cilia‐regulating genes PKD1 (polycystin 1, transient receptor potential channel interacting) or PKD2 , coding for calcium channels (Choi, 2020 ), which have been linked to functional autophagy and maintenance of a physiological catabolic state (Pena‐Oyarzun et al , 2020 ). Cyst expansion observed in the ADPKD mouse model occurs along with an elevated MTOR activity, which is counteracted by treatment with rapamycin (Zafar et al , 2010 ; Choi, 2020 ).…”

Section: Kidney Diseasesmentioning

confidence: 99%

Autophagy in major human diseases

et al. 2021

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Autophagy is a core molecular pathway for the preservation of cellular and organismal homeostasis. Pharmacological and genetic interventions impairing autophagy responses promote or aggravate disease in a plethora of experimental models. Consistently, mutations in autophagy-related processes cause severe human pathologies. Here, we review and discuss preclinical data linking autophagy dysfunction to the pathogenesis of major human disorders including cancer as well as cardiovascular, neurodegenerative, metabolic, pulmonary, renal, infectious, musculoskeletal, and ocular disorders.

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Section: Kidney Diseasesmentioning

confidence: 99%

Autophagy in major human diseases

et al. 2021

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“…However, the role of PC2-dependent autophagy remains to be clarified since it is not involved in cell size regulation, as for MTORC1-AMPK dependent autophagy. Moreover, PC2 regulates autophagy independently of the location in the primary cilium (for a review see [ 120 ]).…”

Section: Autophagy- and Cilia-related Genetic Diseasesmentioning

confidence: 99%

Crosstalk between cilia and autophagy: implication for human diseases

et al. 2022

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Macroautophagy/autophagy is a self-degradative process necessary for cells to maintain their energy balance during development and in response to nutrient deprivation. Autophagic processes are tightly regulated and have been found to be dysfunctional in several pathologies. Increasing experimental evidence points to the existence of an interplay between autophagy and cilia. Cilia are microtubule-based organelles protruding from the cell surface of mammalian cells that perform a variety of motile and sensory functions and, when dysfunctional, result in disorders known as ciliopathies. Indeed, selective autophagic degradation of ciliary proteins has been shown to control ciliogenesis and, conversely, cilia have been reported to control autophagy. Moreover, a growing number of players such as lysosomal and mitochondrial proteins are emerging as actors of the cilia-autophagy interplay. However, some of the published data on the cilia-autophagy axis are contradictory and indicate that we are just starting to understand the underlying molecular mechanisms. In this review, the current knowledge about this axis and challenges are discussed, as well as the implication for ciliopathies and autophagy-associated disorders.

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“…TPCN1, HCN2, SCN9A, GRID1, CHRNA5 and MCOLN3 were also present. These proteins function as voltage-gated calcium channels across lysosomal membranes, native pacemaker currents in heart, sodium-selective channels that allowed Na + to pass as per the electrochemical gradient, channels at synapses and cation channels for inwardly rectifying activity, respectively [68][69][70][71][72][73][74]. The glycine receptor beta protein found was a member of ligand gated chloride channels [75].…”

Section: Role Of Other Significant Hicsmentioning

confidence: 99%

Deciphering the Interactions of SARS-CoV-2 Proteins with Human Ion Channels Using Machine-Learning-Based Methods

et al. 2022

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is accountable for the protracted COVID-19 pandemic. Its high transmission rate and pathogenicity led to health emergencies and economic crisis. Recent studies pertaining to the understanding of the molecular pathogenesis of SARS-CoV-2 infection exhibited the indispensable role of ion channels in viral infection inside the host. Moreover, machine learning (ML)-based algorithms are providing a higher accuracy for host-SARS-CoV-2 protein–protein interactions (PPIs). In this study, PPIs of SARS-CoV-2 proteins with human ion channels (HICs) were trained on the PPI-MetaGO algorithm. PPI networks (PPINs) and a signaling pathway map of HICs with SARS-CoV-2 proteins were generated. Additionally, various U.S. food and drug administration (FDA)-approved drugs interacting with the potential HICs were identified. The PPIs were predicted with 82.71% accuracy, 84.09% precision, 84.09% sensitivity, 0.89 AUC-ROC, 65.17% Matthews correlation coefficient score (MCC) and 84.09% F1 score. Several host pathways were found to be altered, including calcium signaling and taste transduction pathway. Potential HICs could serve as an initial set to the experimentalists for further validation. The study also reinforces the drug repurposing approach for the development of host directed antiviral drugs that may provide a better therapeutic management strategy for infection caused by SARS-CoV-2.

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New emerging roles of Polycystin-2 in the regulation of autophagy

Cited by 8 publications

References 107 publications

Autophagy in major human diseases

Autophagy in major human diseases

Crosstalk between cilia and autophagy: implication for human diseases

Deciphering the Interactions of SARS-CoV-2 Proteins with Human Ion Channels Using Machine-Learning-Based Methods

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