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

George, Ashley A.; Hayden, Sara; Stanton, Gail R.; Brockerhoff, Susan E.

doi:10.1002/bies.201670913

Cited by 72 publications

(59 citation statements)

References 71 publications

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“…This indicates that it is not just the cycling of Rab7 but PI‐4,5‐P 2 itself that is necessary to control this process. This is consistent with the study that shows that loss of Synaptojanin 1 (SynJ1) in zebrafish during the photoreceptor development process leads to the accumulation of autophagosomes .…”

Section: Roles Of Phosphoinositides In Autophagysupporting

confidence: 93%

Phosphoinositides in autophagy: current roles and future insights

2019

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Today, the importance of autophagy in physiological processes and pathological conditions is undeniable. Initially, autophagy merely was described as an evolutionarily conserved mechanism to maintain metabolic homeostasis in times of starvation; however, in recent years it is now apparent that autophagy is a powerful regulator of many facets of cellular metabolism, that its deregulation contributes to various human pathologies, including cancer and neurodegeneration, and that its modulation has considerable potential as a therapeutic approach. Different lipid species, including sphingolipids, sterols, and phospholipids, play important roles in the various steps of autophagy. In particular, there is accumulating evidence indicating the minor group of phospholipids called the phosphoinositides as key modulators of autophagy, including the signaling processes underlying autophagy initiation, autophagosome biogenesis and maturation. In this review, we discuss the known functions to date of the phosphoinositides in autophagy and attempt to summarize the kinases and phosphatases that regulate them as well as the proteins that bind to them throughout the autophagy program. We will also provide examples of how the control of phosphoinositides and their metabolizing enzymes is relevant to understanding many human diseases.Abbreviations ALR, autophagic lysosome reformation; CMT4J, Charcot-Marie-Tooth type 4J; ESI, electron spray ionization; FYCO1, FYVE and coiled-coiled domain-containing 1; GABARAP, gamma-aminobutyric acid receptor-associated protein; HOPS, homotypic fusion and protein sorting; HPLC, high performance liquid chromatography; KO, knockout; MS, mass spectrometry; MS/MS, tandem mass spectrometry; MTM1, Myotubular myopathy 1; MTMRs, myotubularin family of phosphatases; mTORC1, mammalian target of rapamycin complex 1; OCRL, OculoCerebroRenal of Lowe; PDK1, phosphoinositide-dependent kinase-1; PH, pleckstrin homology; PI, phosphatidylinositol; PI-3,5-P 2 , phosphatidylinositol 3,5-bisphosphate; PI-3-P, phosphatidylinositol 3-monophosphate; PI-4,5-P 2 , phosphatidylinositol 4,5-bisphosphate; PI4P5K, phosphatidylinositol-4-phosphate 5-kinase; PI-5-P, phosphatidylinositol 5-monophosphate; PI5P4K, phosphatidylinositol-5-phosphate 4-kinase; PLCd1-PH, PH domain of phospholipase C d1; PLEKHM1, pleckstrin homology domain-containing protein family member 1; PM, plasma membrane; SynJ1, synaptojanin 1; TFEB, transcription factor EB; WIPI, WD-repeat protein interacting with phosphoinositides.

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Section: Roles Of Phosphoinositides In Autophagysupporting

confidence: 93%

Phosphoinositides in autophagy: current roles and future insights

2019

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“…Recent work from our laboratory and the Milosevic laboratory has shown that Endophilin A (EndoA), a protein highly enriched at presynapses, has an unexpected role in autophagy (Murdoch et al, 2016;Soukup et al, 2016). In addition, we also found that the EndoA binding partner Synaptojanin 1 (Synj1), a protein also enriched at synapses, can regulate autophagy (Vanhauwaert et al, 2017), corroborating data from zebrafish (George et al, 2016). Both EndoA and Synj1 have well-established roles in synaptic vesicle endocytosis.…”

Section: Autophagy At the Synapse And Its Effect On Synaptic Functionsupporting

confidence: 86%

Autophagy in the presynaptic compartment in health and disease

Vijayan

Verstreken

2017

Journal of Cell Biology

160

152

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“…Several transgene techniques are applicable to zebrafish models, such as tissue-specific genomic manipulation and the CRISPR system for genome editing. Moreover, several transgenic reporter lines have been used to monitor the autophagy process, including Tg (CMV:EGFP-Mapllc3b) [30], Tg (TαCP:YFP-2XFYVE) [96], and Tg (TαCP:mCherry-GFP-map1 lc3b) [88,95,97]. These techniques promote the understanding of the physiological functions of autophagy in zebrafish.…”

Section: Zebrafish Modelmentioning

confidence: 99%

The Current Understanding of Autophagy in Nanomaterial Toxicity and Its Implementation in Safety Assessment-Related Alternative Testing Strategies

Chen

Liao

et al. 2020

IJMS

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Nanotechnology has rapidly promoted the development of a new generation of industrial and commercial products; however, it has also raised some concerns about human health and safety. To evaluate the toxicity of the great diversity of nanomaterials (NMs) in the traditional manner, a tremendous number of safety assessments and a very large number of animals would be required. For this reason, it is necessary to consider the use of alternative testing strategies or methods that reduce, refine, or replace (3Rs) the use of animals for assessing the toxicity of NMs. Autophagy is considered an early indicator of NM interactions with cells and has been recently recognized as an important form of cell death in nanoparticle-induced toxicity. Impairment of autophagy is related to the accelerated pathogenesis of diseases. By using mechanism-based high-throughput screening in vitro, we can predict the NMs that may lead to the generation of disease outcomes in vivo. Thus, a tiered testing strategy is suggested that includes a set of standardized assays in relevant human cell lines followed by critical validation studies carried out in animals or whole organism models such as C. elegans (Caenorhabditis elegans), zebrafish (Danio rerio), and Drosophila (Drosophila melanogaster)for improved screening of NM safety. A thorough understanding of the mechanisms by which NMs perturb biological systems, including autophagy induction, is critical for a more comprehensive elucidation of nanotoxicity. A more profound understanding of toxicity mechanisms will also facilitate the development of prevention and intervention policies against adverse outcomes induced by NMs. The development of a tiered testing strategy for NM hazard assessment not only promotes a more widespread adoption of non-rodent or 3R principles but also makes nanotoxicology testing more ethical, relevant, and cost- and time-efficient.

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

Cited by 72 publications

References 71 publications

Phosphoinositides in autophagy: current roles and future insights

Phosphoinositides in autophagy: current roles and future insights

Autophagy in the presynaptic compartment in health and disease

The Current Understanding of Autophagy in Nanomaterial Toxicity and Its Implementation in Safety Assessment-Related Alternative Testing Strategies

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