Abstract:Rab7 promotes fusion of autophagosomes and late endosomes with lysosomes. Lőrincz et al. show that Rab2 is critical for the delivery of autophagic and endocytic cargo to lysosomes and for their degradation, and that it promotes autophagosome–lysosome fusion. The results suggest Rab2 and Rab7 coordinately promote autophagic and endosomal degradation and lysosome function.
“…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 Gie e00336 /Df cells, GFP-Rab2 was strongly recruited to the limiting membranes of many of the enlarged late endosomal vacuoles (Figure 10(a)), demonstrating that it does not reach LEs through fusion with lysosomal compartments. It has been suggested that Rab2 arrives to LEs on Golgi-derived vesicles in a HOPS-mediated fusion event and is subsequently quickly released from the membrane [48,79]. Surprisingly, we found that in both Vps39 Δ1 /Df and lt 11 /Df garland cells GFP-Rab2 was still present on the membranes of many of the 2-h tracer-positive and negative enlarged late endosomal vacuoles (Figure 10(a)).10.1080/15548627.2018.1458170-F0010Figure 10.Location of Rab2 in HOPS component and Gie / Arl8 mutants and schematic representation of the function of Rab2 in the endolysosomal system.…”
Section: Resultsmentioning
confidence: 99%
“…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].…”
Section: Discussionmentioning
confidence: 95%
“…However, the observation that the combined loss of Rab2 and Vps39 leads to a slight increase in the severity of the morphological phenotype of the stalled late endosomal compartment in garland cells could imply that Rab2 also interacts with other factors involved in the LE-lysosome transition. In addition, Rab7 is still required for LE-lysosome fusion in Drosophila [79,86]. This suggests that Rab7 may assist in the tethering process, perhaps by recruiting the conserved LE/lysosomal adaptor PLEKHM1 (FlyBase Annotation Symbol CG6613) which is strongly precipitated by activated Drosophila Rab7 [48] and in mammals facilitates LE-lysosome fusion [87,88].…”
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.
“…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 Gie e00336 /Df cells, GFP-Rab2 was strongly recruited to the limiting membranes of many of the enlarged late endosomal vacuoles (Figure 10(a)), demonstrating that it does not reach LEs through fusion with lysosomal compartments. It has been suggested that Rab2 arrives to LEs on Golgi-derived vesicles in a HOPS-mediated fusion event and is subsequently quickly released from the membrane [48,79]. Surprisingly, we found that in both Vps39 Δ1 /Df and lt 11 /Df garland cells GFP-Rab2 was still present on the membranes of many of the 2-h tracer-positive and negative enlarged late endosomal vacuoles (Figure 10(a)).10.1080/15548627.2018.1458170-F0010Figure 10.Location of Rab2 in HOPS component and Gie / Arl8 mutants and schematic representation of the function of Rab2 in the endolysosomal system.…”
Section: Resultsmentioning
confidence: 99%
“…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].…”
Section: Discussionmentioning
confidence: 95%
“…However, the observation that the combined loss of Rab2 and Vps39 leads to a slight increase in the severity of the morphological phenotype of the stalled late endosomal compartment in garland cells could imply that Rab2 also interacts with other factors involved in the LE-lysosome transition. In addition, Rab7 is still required for LE-lysosome fusion in Drosophila [79,86]. This suggests that Rab7 may assist in the tethering process, perhaps by recruiting the conserved LE/lysosomal adaptor PLEKHM1 (FlyBase Annotation Symbol CG6613) which is strongly precipitated by activated Drosophila Rab7 [48] and in mammals facilitates LE-lysosome fusion [87,88].…”
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.
Autophagy is widely considered as a housekeeping mechanism that enables cells to survive stress conditions and, in particular, nutrient deprivation. Autophagy begins with the formation of the phagophore that expands and closes around cytosolic material and damaged organelles destined for degradation. The execution of this complex machinery is guaranteed by the coordinated action of more than 40 ATG (autophagy‐related) proteins that control the entire process at different stages from the biogenesis of the autophagosome to cargo sequestration and fusion with lysosomes. Autophagosome biogenesis occurs at multiple intracellular sites, such as the endoplasmic reticulum (ER) and the plasma membrane. Soon after the formation of the phagophore, the nascent autophagosome progressively grows in size and ultimately closes by recruiting intracellular membranes. In this review, we focus on the contribution of three membrane sources – the ER, the ER–Golgi intermediate compartment, and the Golgi complex – to autophagosome biogenesis and expansion. We also highlight the interplay between the secretory pathway and autophagy in cells when nutrients are scarce.
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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