Inorganic polyphosphate controls cyclophilin B‐mediated collagen folding in osteoblast‐like cells

Khong, Mei Li; Li, Lina; Solesio, María E.; Pavlov, Evgeny; Tanner, Julian A.

doi:10.1111/febs.15249

Cited by 19 publications

(20 citation statements)

References 73 publications

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“…Otherwise, misfolded or partially unfolded proteins are recognized by the GroE chaperonin system that directs them to continue the folding process (O'Neil et al 2018). Other factors intervening in the folding process are the FK506 binding proteins (FKBPs) and cyclophilin B, members of a large family of proteins that possess peptidyl prolyl cis/trans isomerase (PPIase) domains, which alter the conformation of target * Proteins related to exosomal processes proteins (Tong and Jiang 2015;Khong et al 2020). The vesicle-associated membrane protein-associated protein A is localized in the ER/Golgi pathway.…”

Section: Clearing "Recycling" and Protein Synthesis Functionsmentioning

confidence: 99%

More than a simple epithelial layer: multifunctional role of echinoderm coelomic epithelium

et al. 2022

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In echinoderms, the coelomic epithelium (CE) is reportedly the source of new circulating cells (coelomocytes) as well as the provider of molecular factors such as immunity-related molecules. However, its overall functions have been scarcely studied in detail. In this work, we used an integrated approach based on both microscopy (light and electron) and proteomic analyses to investigate the arm CE in the starfish Marthasterias glacialis during different physiological conditions (i.e., non-regenerating and/or regenerating). Our results show that CE cells share both ultrastructural and proteomic features with circulating coelomocytes (echinoderm immune cells). Additionally, microscopy and proteomic analyses indicate that CE cells are actively involved in protein synthesis and processing, and membrane trafficking processes such as phagocytosis (particularly of myocytes) and massive secretion phenomena. The latter might provide molecules (e.g., immune factors) and fluids for proper arm growth/regrowth. No stem cell marker was identified and no pre-existing stem cell was observed within the CE. Rather, during regeneration, CE cells undergo dedifferentiation and epithelial-mesenchymal transition to deliver progenitor cells for tissue replacement. Overall, our work underlines that echinoderm CE is not a “simple epithelial lining” and that instead it plays multiple functions which span from immunity-related roles as well as being a source of regeneration-competent cells for arm growth/regrowth.

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Section: Clearing "Recycling" and Protein Synthesis Functionsmentioning

confidence: 99%

More than a simple epithelial layer: multifunctional role of echinoderm coelomic epithelium

et al. 2022

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“…The unchanged PPIB mRNA-level points to some form of post-transcriptional mechanism underlying the loss of CypB, e.g., increased proteasomal degradation, the induction of autophagy, or microRNA-based repression of protein translation, possibly by the formation of a CypB/CsA complex. CypB harbors an ER retention signal and is thus an endoplasmic reticulum (ER) resident protein ( Derkx and Madrid, 2001 ; Sarro et al., 2020 ; Khong et al., 2020 ). In untreated Huh7 cells (without virus or inhibitor), CypB localizes to the cytoplasm and ER.…”

Section: Discussionmentioning

confidence: 99%

Effects of immunophilin inhibitors and non-immunosuppressive analogs on coronavirus replication in human infection models

Berthold

Ma-Lauer

Chakraborty

et al. 2022

Front. Cell. Infect. Microbiol.

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RationaleHuman coronaviruses (HCoVs) seriously affect human health by causing respiratory diseases ranging from common colds to severe acute respiratory diseases. Immunophilins, including peptidyl-prolyl isomerases of the FK506-binding protein (FKBP) and the cyclophilin family, are promising targets for pharmaceutical inhibition of coronavirus replication, but cell-type specific effects have not been elucidated. FKBPs and cyclophilins bind the immunosuppressive drugs FK506 and cyclosporine A (CsA), respectively.MethodsPrimary human bronchial epithelial cells (phBECs) were treated with CsA, Alisporivir (ALV), FK506, and FK506-derived non-immunosuppressive analogs and infected with HCoV-229E. RNA and protein were assessed by RT-qPCR and immunoblot analysis. Treatment with the same compounds was performed in hepatoma cells (Huh-7.5) infected with HCoV-229E expressing Renilla luciferase (HCoV-229E-RLuc) and the kidney cell line HEK293 transfected with a SARS-CoV-1 replicon expressing Renilla luciferase (SARS-CoV-1-RLuc), followed by quantification of luminescence as a measure of viral replication.ResultsBoth CsA and ALV robustly inhibited viral replication in all models; both compounds decreased HCoV-229E RNA in phBECs and reduced luminescence in HCoV-229E-RLuc-infected Huh7.5 and SARS-CoV-1-RLuc replicon-transfected HEK293. In contrast, FK506 showed inconsistent and less pronounced effects in phBECs while strongly affecting coronavirus replication in Huh-7.5 and HEK293. Two non-immunosuppressive FK506 analogs had no antiviral effect in any infection model.ConclusionThe immunophilin inhibitors CsA and ALV display robust anti-coronaviral properties in multiple infection models, including phBECs, reflecting a primary site of HCoV infection. In contrast, FK506 displayed cell-type specific effects, strongly affecting CoV replication in Huh7.5 and HEK293, but inconsistently and less pronounced in phBECs.

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“…Western Blotting analyses were conducted as previously published ( Baltanas et al, 2013 ; Liu et al, 2019 ; Castro et al, 2020 ; Khong et al, 2020 ). 20 µg of protein per sample was separated using 12% Mini-Protean TGX Precast Gel, and transferred into PVDF membranes.…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial Inorganic Polyphosphate (polyP) Is a Potent Regulator of Mammalian Bioenergetics in SH-SY5Y Cells: A Proteomics and Metabolomics Study

Guitart‐Mampel

Urquiza

Neto

et al. 2022

Front. Cell Dev. Biol.

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Inorganic polyphosphate (polyP) is an ancient, ubiquitous, and well-conserved polymer which is present in all the studied organisms. It is formed by individual subunits of orthophosphate which are linked by structurally similar bonds and isoenergetic to those found in ATP. While the metabolism and the physiological roles of polyP have already been described in some organisms, including bacteria and yeast, the exact role of this polymer in mammalian physiology still remains poorly understood. In these organisms, polyP shows a co-localization with mitochondria, and its role as a key regulator of the stress responses, including the maintenance of appropriate bioenergetics, has already been demonstrated by our group and others. Here, using Wild-type (Wt) and MitoPPX (cells enzymatically depleted of mitochondrial polyP) SH-SY5Y cells, we have conducted a comprehensive study of the status of cellular physiology, using proteomics and metabolomics approaches. Our results suggest a clear dysregulation of mitochondrial physiology, especially of bioenergetics, in MitoPPX cells when compared with Wt cells. Moreover, the effects induced by the enzymatic depletion of polyP are similar to those present in the mitochondrial dysfunction that is observed in neurodegenerative disorders and in neuronal aging. Based on our findings, the metabolism of mitochondrial polyP could be a valid and innovative pharmacological target in these conditions.

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Inorganic polyphosphate controls cyclophilin B‐mediated collagen folding in osteoblast‐like cells

Cited by 19 publications

References 73 publications

More than a simple epithelial layer: multifunctional role of echinoderm coelomic epithelium

More than a simple epithelial layer: multifunctional role of echinoderm coelomic epithelium

Effects of immunophilin inhibitors and non-immunosuppressive analogs on coronavirus replication in human infection models

Mitochondrial Inorganic Polyphosphate (polyP) Is a Potent Regulator of Mammalian Bioenergetics in SH-SY5Y Cells: A Proteomics and Metabolomics Study

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