Autophagy in zebrafish

Varga, Máté; Fodor, Erika; Vellai, Tibor

doi:10.1016/j.ymeth.2014.12.004

Cited by 42 publications

(39 citation statements)

References 95 publications

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“…This observation along with the increased number of PI(3)P structures in nrc a14 cones strongly suggest that there is an increase in the formation of autophagosomes in the absence of SynJ1. Definitive proof of this awaits the development of reagents that recognize pre-autophagosomal structures in zebrafish [60]. …”

Section: Discussionmentioning

confidence: 99%

Arf6 and the 5'phosphatase of synaptojanin 1 regulate autophagy in cone photoreceptors

et al. 2016

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Abnormalities in the ability of cells to properly degrade proteins have been identified in many neurodegenerative diseases. Recent work has implicated Synaptojanin 1 (SynJ1) in Alzheimer’s disease and Parkinson’s disease, although the role of this polyphosphoinositide phosphatase in protein degradation has not been thoroughly described. Here we dissected in vivo the role of SynJ1 in endolysosomal trafficking in zebrafish cone photoreceptors using a SynJ1-deficient zebrafish mutant, nrca14. We found that loss of SynJ1 leads to specific accumulation of late endosomes and autophagosomes early in photoreceptor development. An analysis of autophagic flux revealed that autophagosomes accumulate due to a defect in maturation. In addition we found an increase in vesicles that are highly enriched for PI(3)P, but negative for an early endosome marker in nrca14 cones. A mutational analysis of SynJ1 enzymatic domains found that activity of the 5’ phosphatase, but not the Sac1 domain, is required to rescue both aberrant late endosomes and autophagosomes. Finally, modulating activity of the PI(4,5)P2 regulator, Arf6, rescued the disrupted trafficking pathways in nrca14 cones. Our study describes a specific role for SynJ1 in autophagosomal and endosomal trafficking and provides evidence that PI(4,5)P2 participates in autophagy in a neuronal cell type.

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Section: Discussionmentioning

confidence: 99%

Arf6 and the 5'phosphatase of synaptojanin 1 regulate autophagy in cone photoreceptors

et al. 2016

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“…In our study, rapamycin increasing the longevity of atg7 - and beclin1 -mutated through slowing metabolism and dietary restriction which reduced cellular food demand without malnutrition resulted in metabolic equilibrium. Nevertheless, rapamycin couldn’t stimulate autophagy in mutants throughout the time of treatment as atg7 and beclin1 unable to convert LC3-I intoLC3-II or restore the cargo receptor P62/SQSTM1 which expected to be accountable for the sever deliration of the intestine and strongly correlated with the early death despite treatment (59–61). Those results indicating that beclin1 and atg7 are crucial for rapamycin-induced and that rapamycin depends on the atg5-atg7 dependent autophagy pathway (conventional autophagy) that needs the presence of all ATGs parts including atg7 as well as beclin1 .…”

Section: Discussionmentioning

confidence: 99%

Autophagy-related genesatg7andbeclin1are essential for energy metabolism and survival during the larval-to-juvenile transition stage of zebrafish

Mawed

Zhang

Ren

et al. 2019

Preprint

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High mortality is usually observed during the transition from larvae to juvenile in teleost which is related to the transition from endogenous to exogenous feeding. Autophagy is an evolutionary regulated cellular mechanism highly conserved in eukaryotic organisms to maintain energy homeostasis against stress including starvation. To investigate whether autophagy plays a role during the larval-juvenile transition, we generated atg7 and beclin1 zebrafish mutant lines using CRISPR/Cas9 technology. In this study, both atg7 and beclin1 null zebrafish exhibited a normal body confirmation; nevertheless, they completely died around 15 dpf and 9 dpf respectively. During larval-juvenile transition period, atg7 and beclin1 mutants were unable to cope with the metabolic stress after yolk absorption at 5 dpf and fail to activate autophagy in response to nutrient restriction, and without external feeding, all mutants died nearly at 8 dpf. Dramatic defects in the intestine architecture and metabolic functions in the liver were observed even though providing larvae with an external food supply, suggesting that autophagy isn’t only important during yolk depletion but also within food plenty. Treatment with rapamycin, an activator of autophagy, could effectively extend the survival time of both atg7 and beclin1 null zebrafish through lowering the metabolic rate while it couldn’t activate autophagy in mutants via the canonical pathway. Our findings provided a molecular evidence for the physiological, histological and metabolic changes that occur during the transition process from the larval to the juvenile stages and the chief role of autophagy on the body metabolism during these turning milestones.Author summaryZebrafish Danio rerio has emergrd one of the most powerful research models for studying genes expression during early embryogenesis and postnatal development. On the basis of the cell mechanisms, Macroautphagy, a natural regulated pathway disassembles unnecessary or dysfunctional components orchestrated by more than 36 autophagy related-genes conserved from yeast to mammals. Among those genes are atg7 and beclin1 which have been proved to play an important role in regulating post natal development in some mammals however their roles during zebrafish development still unedited. During this research, CRISPER/CAS9 were adopted to know atg7 and beclin1 knockout effects on the mutants’ metabolism during shifting from maternal yolk acquisition to exogenous feeding and the role of autophagy during the larvae to pre-juvenile development. Herein, we found out that larvae couldn’t abandon autophagy in both fasting and feeding conditions as larvae died earlier before pre-juvenile development despite feeding declaring the importance of autophagy not only to provide the cell with essential nutrients during starvation but also to get rid of cargos inside the eukaryotic cells. Briefly, if the larvae didn’t recycle those cargos due to autophagy perturbations, they will die despite providing suitable conditions including food and acclimatization.

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“…The ubiquitin-proteasome system and the autophagy system are two of the most important protein degradation machineries involved in cell death, cell survival, and cell fate conversion during embryonic development and adult tissue regeneration2425. During zebrafish caudal fin regeneration, autophagy is activated in the blastema, while inactivation of autophagy stimulates mesenchymal blastema cells to undergo apoptosis26.…”

Section: Discussionmentioning

confidence: 99%

Tissue Extract Fractions from Starfish Undergoing Regeneration Promote Wound Healing and Lower Jaw Blastema Regeneration of Zebrafish

Dai

Prithiviraj

Gan

et al. 2016

Sci Rep

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Natural bioactive materials provide an excellent pool of molecules for regenerative therapy. In the present study, we amputate portions of the arms of Archaster typicus starfish, extract and separate the active biomaterials, and compare the effects of each fraction on in vitro wound healing and in vivo lower jaw regeneration of zebrafish. Compared with crude extract, normal hexane fractions (NHFs) have a remarkable effect on cellular proliferation and collective migration, and exhibit fibroblast-like morphology, while methanol-water fractions (MWFs) increase cell size, cell-cell adhesion, and cell death. Relative to moderate mitochondrialand lysosomal aggregation in NHFs-cultured cells, MWFs-cultured cells contain more and bigger lysosomal accumulations and clump detachment. The in vivo zebrafish lower jaw regeneration model reveals that NHFs enhance blastema formation and vasculogenesis, while MWFs inhibit fibrogenesis and induce cellular transformation. Gene expression analyses indicate that NHFs and MWFs separately activate blastema-characteristic genes as well as those genes-related to autophagy, proteasome, and apoptosis either during cell scratch healing or ganciclovir-induced apoptosis. Our results suggest that bioactive compounds from NHFs and MWFs could induce blastema formation and remodeling, respectively, and prevent tissue overgrowth.

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Autophagy in zebrafish

Cited by 42 publications

References 95 publications

Arf6 and the 5'phosphatase of synaptojanin 1 regulate autophagy in cone photoreceptors

Arf6 and the 5'phosphatase of synaptojanin 1 regulate autophagy in cone photoreceptors

Autophagy-related genesatg7andbeclin1are essential for energy metabolism and survival during the larval-to-juvenile transition stage of zebrafish

Tissue Extract Fractions from Starfish Undergoing Regeneration Promote Wound Healing and Lower Jaw Blastema Regeneration of Zebrafish

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