Loss of <i>Drosophila</i> Vps16A enhances autophagosome formation through reduced Tor activity

Takáts, Szabolcs; Varga, Ágnes; Pircs, Karolina; Juhász, Gábor

doi:10.1080/15548627.2015.1059559

Cited by 12 publications

(9 citation statements)

References 34 publications

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“…TOR activity can be analyzed by detection of phosphorylation levels of direct TOR targets such as S6K and 4EBP1. Commercial antibodies are available for this purpose ( Table 1 ) [ 46 , 54 , 70 ]. These experiments can provide important insight into the regulation of autophagy induction in a given setting.…”

Section: Advantages and Limitations Of Commonly Used Autophagy Assmentioning

confidence: 99%

Exploring Autophagy in Drosophila

Lőrincz

Mauvezin

Juhász

2017

Cells

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Autophagy is a catabolic process in eukaryotic cells promoting bulk or selective degradation of cellular components within lysosomes. In recent decades, several model systems were utilized to dissect the molecular machinery of autophagy and to identify the impact of this cellular “self-eating” process on various physiological and pathological processes. Here we briefly discuss the advantages and limitations of using the fruit fly Drosophila melanogaster, a popular model in cell and developmental biology, to apprehend the main pathway of autophagy in a complete animal.

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Section: Advantages and Limitations Of Commonly Used Autophagy Assmentioning

confidence: 99%

Exploring Autophagy in Drosophila

Lőrincz

Mauvezin

Juhász

2017

Cells

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“…Others and we have previously shown that Drosophila is an excellent model to study miniCORVET and HOPS mediated vesicular trafficking processes, including endosome maturation in nephrocytes, autophagosome-lysosome fusion in fat cells, crinophagy in salivary glands and eye pigment granule biogenesis (Akbar et al, 2009; Csizmadia et al, 2018; Lindmo et al, 2006; Lőrincz et al, 2016a; Lőrincz et al, 2017a; Lőrincz et al, 2016b; Lőrincz et al, 2017b; Pulipparacharuvil et al, 2005; Sevrioukov et al, 1999; Takáts et al, 2014; Takáts et al, 2015; Warner et al, 1998). We now aimed to answer the question whether the overexpression of CORVET-specific Vps8 or its HOPS-specific counterpart Vps41 could affect HOPS or CORVET dependent processes, respectively, and if so how.…”

Section: Introductionmentioning

confidence: 99%

Vps8 overexpression inhibits HOPS-dependent trafficking routes by outcompeting Vps41/Lt

Lőrincz

Kenéz

Tóth

et al. 2019

eLife

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Two related multisubunit tethering complexes promote endolysosomal trafficking in all eukaryotes: Rab5-binding CORVET that was suggested to transform into Rab7-binding HOPS. We have previously identified miniCORVET, containing Drosophila Vps8 and three shared core proteins, which are required for endosome maturation upstream of HOPS in highly endocytic cells (Lőrincz et al., 2016a). Here, we show that Vps8 overexpression inhibits HOPS-dependent trafficking routes including late endosome maturation, autophagosome-lysosome fusion, crinophagy and lysosome-related organelle formation. Mechanistically, Vps8 overexpression abolishes the late endosomal localization of HOPS-specific Vps41/Lt and prevents HOPS assembly. Proper ratio of Vps8 to Vps41 is thus critical because Vps8 negatively regulates HOPS by outcompeting Vps41. Endosomal recruitment of miniCORVET- or HOPS-specific subunits requires proper complex assembly, and Vps8/miniCORVET is dispensable for autophagy, crinophagy and lysosomal biogenesis. These data together indicate the recruitment of these complexes to target membranes independent of each other in Drosophila, rather than their transformation during vesicle maturation.

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“…Thirdly, when we simultaneously silenced the TGN‐related retrograde transport factor, Syx16 and the nonspecific HOPS tethering complex component, Vps16a (previously shown to be required for crinophagy 12 ), these large and acidic structures were not further observed, only immature but non‐acidic small glue granules were detected in the salivary gland cells of both wandering and prepupal developmental stages (Figures 5G, H and 6D). Importantly, Syx16 and Vps16a are not required for microautophagy, but in addition of crinophagy, Vps16a is necessary for autophagosome‐lysosome fusion too 56,64 . During ultrastructural analysis of the salivary gland cells containing Vps16a‐Syx16 double RNAi, we experienced that, these cells never included immature and small glue granules inside of their autophagosomes.…”

Section: Discussionmentioning

confidence: 96%

“…12 Interestingly, when Vps16a and Syx16 were silenced simultaneously, cells isolated from both the wandering and prepupal stages contained mainly intact, small glue granules and only a few but abnormally tiny acidic crinosomes (Figures 5G, H and 6D). It is important to note that, depletion of Vps16a may accumulate autophagosomes in the cytoplasm, 56 even so the immature small glue granules never occur inside of autophagosomes in Vps16a-Syx16 double RNAi salivary gland cells.…”

Section: Examination Of Developmental Programdependent and Independen...mentioning

confidence: 99%

Developmental program‐independent secretory granule degradation in larval salivary gland cells of Drosophila

Csizmadia

Dósa

Farkas

et al. 2022

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Both constitutive and regulated secretion require cell organelles that are able to store and release the secretory cargo. During development, the larval salivary gland of Drosophila initially produces high amount of glue‐containing small immature secretory granules, which then fuse with each other and reach their normal 3–3.5 μm in size. Following the burst of secretion, obsolete glue granules directly fuse with late endosomes or lysosomes by a process called crinophagy, which leads to fast degradation and recycling of the secretory cargo. However, hindering of endosome‐to‐TGN retrograde transport in these cells causes abnormally small glue granules which are not able to fuse with each other. Here, we show that loss of function of the SNARE genes Syntaxin 16 (Syx16) and Synaptobrevin (Syb), the small GTPase Rab6 and the GARP tethering complex members Vps53 and Scattered (Vps54) all involved in retrograde transport cause intense early degradation of immature glue granules via crinophagy independently of the developmental program. Moreover, silencing of these genes also provokes secretory failure and accelerated crinophagy during larval development. Our results provide a better understanding of the relations among secretion, secretory granule maturation and degradation and paves the way for further investigation of these connections in other metazoans.

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Loss of Drosophila Vps16A enhances autophagosome formation through reduced Tor activity

Cited by 12 publications

References 34 publications

Exploring Autophagy in Drosophila

Exploring Autophagy in Drosophila

Vps8 overexpression inhibits HOPS-dependent trafficking routes by outcompeting Vps41/Lt

Developmental program‐independent secretory granule degradation in larval salivary gland cells of Drosophila

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