<scp>FK506</scp>‐binding protein 5 regulates cell quiescence‐proliferation decision in zebrafish epithelium

Li, Yingxiang; Liu, Chengdong; Bai, Xuanxuan; Li, Mingyu; Duan, Cunming

doi:10.1002/1873-3468.14670

Cited by 3 publications

(2 citation statements)

References 56 publications

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“…As shown in Figures 2C, D , BMS-754807 reduced trpv6 mRNA levels to the sibling levels, suggesting that loss of Stc1a increases Trpv6 expression via an IGF signaling-dependent mechanism. Recently, we have discovered that serum- and glucocorticoid-regulated kinase 1 (Sgk1) acts downstream in the IGF-Akt-Tor signaling pathway in NaR cells ( 35 , 36 ). Studies in culture mammalian cells suggest that SGK1 up-regulates the expression of several ion channels and transporters, including the epithelial Ca 2+ channels TRPV5 and TRPV6 ( 37 ).…”

Section: Resultsmentioning

confidence: 99%

Stanniocalcin 1a regulates organismal calcium balance and survival by suppressing Trpv6 expression and inhibiting IGF signaling in zebrafish

Li,

Wang

et al. 2023

Front. Endocrinol.

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Stanniocalcin 1 (Stc1) is well known for its role in regulating calcium uptake in fish by acting on ionocytes or NaR cells. A hallmark of NaR cells is the expression of Trpv6, a constitutively open calcium channel. Recent studies in zebrafish suggest that genetical deletion of Stc1a and Trpv6 individually both increases IGF signaling and NaR cell proliferation. While trpv6-/- fish suffered from calcium deficiency and died prematurely, stc1a-/- fish had elevated body calcium levels but also died prematurely. The relationship between Stc1a, Trpv6, and IGF signaling in regulating calcium homeostasis and organismal survival is unclear. Here we report that loss of Stc1a increases Trpv6 expression in NaR cells in an IGF signaling-dependent manner. Treatment with CdCl2, a Trpv6 inhibitor, reduced NaR cell number in stc1a-/- fish to the sibling levels. Genetic and biochemical analysis results suggest that Stc1a and Trpv6 regulate NaR cell proliferation via the same IGF pathway. Alizarin red staining detected abnormal calcium deposits in the yolk sac region and kidney stone-like structures in stc1a-/- fish. Double knockout or pharmacological inhibition of Trpv6 alleviated these phenotypes, suggesting that Stc1a inhibit epithelial Ca2+ uptake by regulating Trpv6 expression and activity. stc1a-/- mutant fish developed cardiac edema, body swelling, and died prematurely. Treatment of stc1a-/- fish with CdCl2 or double knockout of Trpv6 alleviated these phenotypes. These results provide evidence that Stc1a regulates calcium homeostasis and organismal survival by suppressing Trpv6 expression and inhibiting IGF signaling in ionocytes.

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Section: Resultsmentioning

confidence: 99%

Stanniocalcin 1a regulates organismal calcium balance and survival by suppressing Trpv6 expression and inhibiting IGF signaling in zebrafish

Li,

Wang

et al. 2023

Front. Endocrinol.

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“…In males Fkbp5 and Klf15, two known GR targets (56,57) have the same expression profile. FKBP5 inhibits Cdk4 and thereby the cell cycle to promote myogenic differentiation and has been shown to be antiproliferative in multiple models (58)(59)(60)(61). Klf15 is also a negative regulator of proliferation (62,63) and has been shown to regulate myotube size downstream of GCs (64), however, a role for this factor in the regulation of MuSC function has not been described.…”

Section: Discussionmentioning

confidence: 99%

The glucocorticoid receptor is a critical regulator of muscle satellite cell quiescence

Rajgara,

AlSudais,

Saleh

et al. 2023

Preprint

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Glucocorticoids are powerful anti-inflammatory medications that are associated with muscle atrophy. The effect of glucocorticoids in myofibers is well-studied, yet the role of the glucocorticoid receptor (GR), the primary mediator of glucocorticoid transcriptional responses, and the impact of glucocorticoid signalling in muscle stem cells (MuSCs), the adult progenitors responsible for regeneration, remain unknown. We developed a conditional null mouse model to knock out glucocorticoid receptor (GR) expression in MuSCs (GRMuSC-/-) and established that while GR is dispensable for muscle regeneration, it is a critical regulator of MuSC homeostasis. Loss of GR significantly increased cycling MuSCs as compared to controls in injury-naïve mice and on single EDL myofiber cultures, and as such, loss of GR in MuSCs leads to precocious activation and subsequent proliferation as compared to controls. Bulk RNA-sequencing fromin situfixed MuSCs from injury-naïve GRMuSC-/-muscle identified a gene signature consistent with cells that have exited quiescence and undergone activation, with evidence of sexual dimorphism. Using ATAC-seq and footprinting we identify putative GR targets that promote quiescence. Thus, we advance the GR as a previously unrecognized crucial transcriptional regulator of gene expression in MuSCs whose activity is highest in quiescent cells and is essential to maintain that state.

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A decrease in Fkbp52 alters autophagosome maturation and A152T-tau clearance in vivo

Lesport,

Commeau,

Genet

et al. 2024

Front. Cell. Neurosci.

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The failure of the autophagy-lysosomal pathway to clear the pathogenic forms of Tau exacerbates the pathogenesis of tauopathies. We have previously shown that the immunophilin FKBP52 interacts both physically and functionally with Tau, and that a decrease in FKBP52 protein levels is associated with Tau deposition in affected human brains. We have also shown that FKBP52 is physiologically present within the lysosomal system in healthy human neurons and that a decrease in FKBP52 expression alters perinuclear lysosomal positioning and Tau clearance during Tau-induced proteotoxic stress in vitro. In this study, we generate a zebrafish fkbp4 loss of function mutant and show that axonal retrograde trafficking of Lamp1 vesicles is altered in this mutant. Moreover, using our transgenic HuC::mCherry-EGFP-LC3 line, we demonstrate that the autophagic flux is impaired in fkbp4 mutant embryos, suggesting a role for Fkbp52 in the maturation of autophagic vesicles. Alterations in both axonal transport and autophagic flux are more evident in heterozygous rather than homozygous fkbp4 mutants. Finally, taking advantage of the previously described A152T-Tau transgenic fish, we show that the clearance of pathogenic A152T-Tau mutant proteins is slower in fkbp4+/− mutants in comparison to fkbp4+/+ larvae. Altogether, these results indicate that Fkbp52 is required for the normal trafficking and maturation of lysosomes and autophagic vacuoles along axons, and that its decrease is sufficient to hinder the clearance of pathogenic Tau in vivo.

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FK506‐binding protein 5 regulates cell quiescence‐proliferation decision in zebrafish epithelium

Cited by 3 publications

References 56 publications

Stanniocalcin 1a regulates organismal calcium balance and survival by suppressing Trpv6 expression and inhibiting IGF signaling in zebrafish

Stanniocalcin 1a regulates organismal calcium balance and survival by suppressing Trpv6 expression and inhibiting IGF signaling in zebrafish

The glucocorticoid receptor is a critical regulator of muscle satellite cell quiescence

A decrease in Fkbp52 alters autophagosome maturation and A152T-tau clearance in vivo

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