Genetic screen in Drosophila muscle identifies autophagy-mediated T-tubule remodeling and a Rab2 role in autophagy

Fujita, Naonobu; Huang, Wilson; Lin, Tzu Han; Groulx, Jean Francois; Jean, Steve; Nguyen, Jen; Kuchitsu, Yoshihiko; Koyama-Honda, Ikuko; Mizushima, Noboru; Fukuda, Mitsunori; Kiger, Amy A.

doi:10.7554/elife.23367

Cited by 96 publications

(91 citation statements)

References 88 publications

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“…While this work was in revision, two papers have been published describing the role of Rab2 in LE-lysosome fusion and autophagosome-lysosome fusion, respectively [79,89]. Lőrincz et al use Drosophila garland cells and fat bodies and human cells to essentially show the same requirement for Rab2 in LE-lysosome fusion and autophagy described here [79].…”

Section: Discussionmentioning

confidence: 94%

“…In Drosophila , Rab2 and both Lt/Vps41 [29] and Vps39, but not Gie/Arl8, are necessary for efficient delivery of these carriers. In addition, Rab2 and the HOPS complex are required for the fusion of autophagosomes to LEs and lysosomes [30,31,79,89]. In contrast, the AP-3 and HOPS complexes, but not Rab2, are necessary for trafficking to LROs such as pigment granules [30,58–63].…”

Section: Resultsmentioning

confidence: 99%

“…Lőrincz et al use Drosophila garland cells and fat bodies and human cells to essentially show the same requirement for Rab2 in LE-lysosome fusion and autophagy described here [79]. Fujita et al describe the dependence of autophagic clearance and autophagosome delivery to endosomal and lysosomal compartments on Rab2 in Drosophila and mouse embryonic fibroblasts [89]. The picture that emerges from our work and the findings of Lőrincz et al and Fujita et al is that Rab2 controls all major heterotypic fusion processes at the LE, i.e.…”

Section: Discussionmentioning

confidence: 97%

“…Lőrincz et al argue that Rab2 traffics to LEs on the membranes of Golgi-derived vesicles that fuse with Rab7-positive LEs in a HOPS-dependent manner [79]. Likewise, Fujita et al suggest that Rab2 is present on the outer membrane of autophagosomes that fuse to Rab7-positive LEs or lysosomes [89]. However, as mentioned, we observe that in garland cells Rab2 is bound to the limiting membrane of LE vacuoles even when HOPS-mediated vesicular fusion was blocked by the absence of Vps39 or Lt/Vps41, and when macroautophagy was abrogated by the absence of Atg7.…”

Section: Discussionmentioning

confidence: 99%

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Drosophila Rab2 controls endosome-lysosome fusion and LAMP delivery to late endosomes

2018

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Rab2 is a conserved Rab GTPase with a well-established role in secretory pathway function and phagocytosis. Here we demonstrate that Drosophila Rab2 is recruited to late endosomal membranes, where it controls the fusion of LAMP-containing biosynthetic carriers and lysosomes to late endosomes. In contrast, the lysosomal GTPase Gie/Arl8 is only required for late endosome-lysosome fusion, but not for the delivery of LAMP to the endocytic pathway. We also find that Rab2 is required for the fusion of autophagosomes to the endolysosomal pathway, but not for the biogenesis of lysosome-related organelles. Surprisingly, Rab2 does not rely on HOPS-mediated vesicular fusion for recruitment to late endosomal membranes. Our work suggests that Drosophila Rab2 is a central regulator of the endolysosomal and macroautophagic/autophagic pathways by controlling the major heterotypic fusion processes at the late endosome.

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Section: Discussionmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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Drosophila Rab2 controls endosome-lysosome fusion and LAMP delivery to late endosomes

2018

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“…Its GAP ornithine aminotransferase-like 1 (OATL1, also known as TBC1D25) is recruited onto autophagosomes through direct interaction with ATG8, and OATL1 overexpression has been shown to inhibit autophagosome-lysosome fusion (Itoh et al, 2011). It has been recently shown that during T-tubule remodeling in Drosophila, Rab2 localizes to completed autophagosomes and interacts with the HOPS complex to promote autophagosomelysosome fusion (Fujita et al, 2017). These results suggest that, although Rab7 plays a pivotal role during autophagosome-lysosome fusion, further small GTPases are involved in this process and otherso-far unappreciated -functions of members of this protein family might be discovered in future.…”

Section: Rab Proteinsmentioning

confidence: 99%

New insights into autophagosome–lysosome fusion

Nakamura

Yoshimori

2017

Journal of Cell Science

378

298

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Macroautophagy (autophagy) is a highly conserved intracellular degradation system that is essential for homeostasis in eukaryotic cells. Due to the wide variety of the cytoplasmic targets of autophagy, its dysregulation is associated with many diseases in humans, such as neurodegenerative diseases, heart disease and cancer. During autophagy, cytoplasmic materials are sequestered by the autophagosome -a double-membraned structure -and transported to the lysosome for digestion. The specific stages of autophagy are induction, formation of the isolation membrane (phagophore), formation and maturation of the autophagosome and, finally, fusion with a late endosome or lysosome. Although there are significant insights into each of these steps, the mechanisms of autophagosomelysosome fusion are least understood, although there have been several recent advances. In this Commentary, we will summarize the current knowledge regarding autophagosome-lysosome fusion, focusing on mammals, and discuss the remaining questions and future directions of the field.

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Crosstalk between Autophagy and Nanomaterials: Internalization, Activation, Termination

Wei

Duan

2018

Adv. Biosys.

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NMs, SiO 2 -based NMs, lipid-based NMs, polymer-based NMs, polyethylene glycol (PEG)-based NMs, and other types NMs. Alternatively, according to the physical and chemical properties of NMs, they can be classified into soft NMs, referring to lipidor polymer-based NMs, and hard NMs such as mental-or carbon-based NMs.With the development of nanotechnology, these materials have been widely applied in various fields. [3] For example, ZnO nanoparticles (NPs) can serve as antimicrobial agents; [4] TiO 2 NPs are used in sunscreen lotions; [5] lipid/polymeric-based NPs are applied in drug/gene delivery; [6] QDs are used as florescent probes; [7] and magnetic NPs are applied in magnetic resonance imaging. [8] The NMs not only effectively enhance cellular and subcellular targeting of drugs and the effect of imaging, but also rise the attention on the importance of affirming the effect of NMs on biological systems. It has been recognized that NMs are capable of modulating autophagy. The modulation of NMs on autophagy may be beneficial, since the combinative effect of the NMs' features and autophagy functions is capable of enhancing the accuracy of diagnosis and efficiency of therapies. For example, AgNPs could be a fascinating tool in infections and antimicrobial immunity in that the NM-phagy can modulate the antiviral/antibacterial defenses. [9] In this process, AgNPs lead to the disorganization of mitochondrial network and contribute to the modulation of autophagy (both Rab9-dependent alternative autophagy and Atg-5-dependent classical autophagy) by blocking the autophagic flux. Additionally, AgNPs can reduce the production of CCL-5 and interferon (IFN)-β in influenza-infected cells through the Rab9-dependent alternative autophagy.Autophagy, a "self-digestion" biological process of cellular degradation, is induced when cells are subjected to unfavorable factors, including starvation or drug treatments, accumulation of the damaged organelles, and misfolded proteins. The autophagic process refers to the cargo encompassed into autophagosome and delivery of cargo to lysosomes to degrade and to release macromolecules back into the cytosol. [10] If the "self-digestion" gets out of control, the autophagy dysfunction, including excessive autophagy induction or suppression of autophagy flux, will induce serious diseases, such as cancer, neurodegenerative diseases, immunological diseases, innate turbulence, and even cell death. [11] Therefore, autophagy is Nanomaterials (NMs) are comprehensively applied in biomedicine due to their unique physical and chemical properties. Autophagy, as an evolutionarily conserved cellular quality control process, is closely associated with the effect of NMs on cells. In this review, the recent advances in NM-induced/ inhibited autophagy (NM-phagy) are summarized, with an aim to present a comprehensive description of the mechanisms of NM-phagy from the perspective of internalization, activation, and termination, thereby bridging autophagy and nanomaterials. Several possible mechanisms are extensively ...

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Genetic screen in Drosophila muscle identifies autophagy-mediated T-tubule remodeling and a Rab2 role in autophagy

Cited by 96 publications

References 88 publications

Drosophila Rab2 controls endosome-lysosome fusion and LAMP delivery to late endosomes

Drosophila Rab2 controls endosome-lysosome fusion and LAMP delivery to late endosomes

New insights into autophagosome–lysosome fusion

Crosstalk between Autophagy and Nanomaterials: Internalization, Activation, Termination

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