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Different mechanisms of endosomal and autophagosomal PI3P formation. (A, B) GFP-FYVE marked PI3P-positive endosomes are absent from UVRAG mutant fat cell clones (dsRed-cells in panel A) of well-fed L3 larvae. However, starvation induces the generation of GFP-FYVE dots in UVRAG loss of function cells (dsRed-) in a similar number as in dsRed+ controls (B). (C-D) The number of GFP-FYVE positive endosomes is similar in well-fed Atg14 mutant clones (dsRed-) and dsRed+ control cells (C). In contrast, Atg14 mutant cells contain fewer GFP-FYVE dots than control cells under starvation conditons (D). (E) Starvation-induced formation of 3xmCherry-Atg8a labeled autophagic structures is similar in UVRAG null mutant clones (GFP+) and control cells (GFP-). (F) On the contrary, a complete inhibition of punctate 3xmCherry-Atg8a is observed in GFP+ Atg14 mutant cells compared to neighboring GFP-controls. (G, H) Quantification of data shown in A-D (G) and E-F (H); n=10/genotype. (I) Western blots reveal that UVRAG mutants show mild, while Atg14 mutants show strong accumulation of the autophagic cargo p62 both in well-fed and starved larvae. Tubulin serves as a loading control. Clone cells in grayscale panels of A-F are outlined in magenta. Scale bar in A equals 20 μm for A-F.
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The small GTPase Rab5 promotes recruitment of the Ccz1-Mon1 guanosine exchange complex to endosomes to activate Rab7, which facilitates endosome maturation and fusion with lysosomes. How these factors function during autophagy is incompletely understood. Here we show that autophagosomes accumulate due to impaired fusion with lysosomes upon loss of...
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... clarify the role of the Atg14 and UVRAG complexes during PI3P formation, we targeted the Atg14 locus using Cas9 mutagenesis. A 790 bp deletion was identified that begins 17 bp upstream of the start ATG, and deletes nearly the first half of the protein coding sequence (Figure S6A, B). Flies homozygous for this Atg14[d13] allele accumulated high amounts of the specific autophagic cargo p62, and mutant fat cell clones completely lacked LTR-positive autolysosomes ( Figure S6C, D), similar to previously described Atg mutants. ...
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... 790 bp deletion was identified that begins 17 bp upstream of the start ATG, and deletes nearly the first half of the protein coding sequence (Figure S6A, B). Flies homozygous for this Atg14[d13] allele accumulated high amounts of the specific autophagic cargo p62, and mutant fat cell clones completely lacked LTR-positive autolysosomes ( Figure S6C, D), similar to previously described Atg mutants. Importantly, the expression of an endogenous promoter-driven, C-terminally HA-tagged Atg14 transgene on the Atg14 mutant background suppresses the buildup of p62 (Figure S6C), indicating that the autophagy defect is solely due to loss of Atg14 in these animals. ...
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... homozygous for this Atg14[d13] allele accumulated high amounts of the specific autophagic cargo p62, and mutant fat cell clones completely lacked LTR-positive autolysosomes ( Figure S6C, D), similar to previously described Atg mutants. Importantly, the expression of an endogenous promoter-driven, C-terminally HA-tagged Atg14 transgene on the Atg14 mutant background suppresses the buildup of p62 (Figure S6C), indicating that the autophagy defect is solely due to loss of Atg14 in these animals. ...
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... used our new Atg14[d13] and the recently described UVRAG null mutant (Takats et al., 2014) alleles to test how these affect Vsp34 kinase activity and autophagy. UVRAG [LL] mutant fat cells showed a complete lack of PI3P under well-fed conditions ( Figure 6A, G), while starvation readily induced GFP-FYVE dots both in control and UVRAG loss of function cells (Figure 6B, G). Cells lacking Atg14 showed an opposite phenotype: the number of GFP-FYVE structures was not statistically significantly different from neighboring control cells in the fed state ( Figure 6C, G), whereas upon starvation the generation of PI3P- positive vesicles was strongly decreased in Atg14[d13] mutant clones ( Figure 6D, G). ...
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... used our new Atg14[d13] and the recently described UVRAG null mutant (Takats et al., 2014) alleles to test how these affect Vsp34 kinase activity and autophagy. UVRAG [LL] mutant fat cells showed a complete lack of PI3P under well-fed conditions ( Figure 6A, G), while starvation readily induced GFP-FYVE dots both in control and UVRAG loss of function cells (Figure 6B, G). Cells lacking Atg14 showed an opposite phenotype: the number of GFP-FYVE structures was not statistically significantly different from neighboring control cells in the fed state ( Figure 6C, G), whereas upon starvation the generation of PI3P- positive vesicles was strongly decreased in Atg14[d13] mutant clones ( Figure 6D, G). ...
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... [LL] mutant fat cells showed a complete lack of PI3P under well-fed conditions ( Figure 6A, G), while starvation readily induced GFP-FYVE dots both in control and UVRAG loss of function cells (Figure 6B, G). Cells lacking Atg14 showed an opposite phenotype: the number of GFP-FYVE structures was not statistically significantly different from neighboring control cells in the fed state ( Figure 6C, G), whereas upon starvation the generation of PI3P- positive vesicles was strongly decreased in Atg14[d13] mutant clones ( Figure 6D, G). We also tested whether the formation of 3xmCherry-Atg8a-positive structures is affected in UVRAG and Atg14 mutants. ...
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... [LL] mutant fat cells showed a complete lack of PI3P under well-fed conditions ( Figure 6A, G), while starvation readily induced GFP-FYVE dots both in control and UVRAG loss of function cells (Figure 6B, G). Cells lacking Atg14 showed an opposite phenotype: the number of GFP-FYVE structures was not statistically significantly different from neighboring control cells in the fed state ( Figure 6C, G), whereas upon starvation the generation of PI3P- positive vesicles was strongly decreased in Atg14[d13] mutant clones ( Figure 6D, G). We also tested whether the formation of 3xmCherry-Atg8a-positive structures is affected in UVRAG and Atg14 mutants. ...
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... also tested whether the formation of 3xmCherry-Atg8a-positive structures is affected in UVRAG and Atg14 mutants. In cells lacking UVRAG, the number of 3xmCherry-Atg8a dots was comparable to control cells ( Figure 6E, H), in line with our recent report. In contrast, autophagic structures were absent from Atg14 mutant fat cell clones (Figure 6F,H). ...
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... cells lacking UVRAG, the number of 3xmCherry-Atg8a dots was comparable to control cells ( Figure 6E, H), in line with our recent report. In contrast, autophagic structures were absent from Atg14 mutant fat cell clones (Figure 6F,H). We also tested the autophagosomal localization of Mon1 in wild type and mutant backgrounds to more directly support these findings. ...
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... also tested the autophagosomal localization of Mon1 in wild type and mutant backgrounds to more directly support these findings. As expected, we could detect the presence of Mon1-HA on endogenous Atg8a-positive autophagosomes in both control and UVRAG mutant fat cells (Figure S6E, F). In contrast, Atg14 mutant cells lacked endogenous Atg8a-positive autophagosomes, whereas Mon1-HA dots could still be observed ( Figure S6G). ...
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... expected, we could detect the presence of Mon1-HA on endogenous Atg8a-positive autophagosomes in both control and UVRAG mutant fat cells (Figure S6E, F). In contrast, Atg14 mutant cells lacked endogenous Atg8a-positive autophagosomes, whereas Mon1-HA dots could still be observed ( Figure S6G). ...
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... we tested the level of p62 in fed and starved larvae in two independent UVRAG null mutant lines as well as in Atg14[d13] homozygotes. We found large-scale accumulation of p62 in Atg14 mutants under both conditions (Figure 6I), altogether indicating that the Atg14 complex is required for PI3P-positive autophagosome formation. UVRAG loss of function lines showed a moderate increase of p62 compared with control animals ( Figure 6I). ...
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... found large-scale accumulation of p62 in Atg14 mutants under both conditions (Figure 6I), altogether indicating that the Atg14 complex is required for PI3P-positive autophagosome formation. UVRAG loss of function lines showed a moderate increase of p62 compared with control animals ( Figure 6I). These findings are consistent with our recent study, in which we showed that although the loss of UVRAG does not inhibit autophagosome formation or fusion, it impairs the lysosomal degradation of autophagic cargo (Takats et al., 2014), which is likely responsible for the increase in the amount of p62. ...
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The yeast vacuole is a vital organelle, which is required for the degradation of aberrant intracellular or extracellular substrates and the recycling of the resulting nutrients as newly available building blocks for the cellular metabolism. Like the plant vacuole or the mammalian lysosome, the yeast vacuole is the destination of biosynthetic traffi...
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... RAB7A is recruited to mitochondria following mitochondrial damage in a process regulated by RABGEF1 and TBC1D15/ 17, a RAB7A GEF and GAP, respectively (Yamano et al., 2018;Hegedűs et al., 2016). RAB phosphorylation has emerged as a major theme in the regulation of membrane traffic and PD, in particular (Pfeffer, 2023). ...
Activation of PINK1 and Parkin in response to mitochondrial damage initiates a response that includes phosphorylation of RAB7A at Ser72. Rubicon is a RAB7A binding negative regulator of autophagy. The structure of the Rubicon:RAB7A complex suggests that phosphorylation of RAB7A at Ser72 would block Rubicon binding. Indeed, in vitro phosphorylation of RAB7A by TBK1 abrogates Rubicon:RAB7A binding. Pacer, a positive regulator of autophagy, has an RH domain with a basic triad predicted to bind an introduced phosphate. Consistent with this, Pacer-RH binds to phosho-RAB7A but not to unphosphorylated RAB7A. In cells, mitochondrial depolarization reduces Rubicon:RAB7A colocalization whilst recruiting Pacer to phospho-RAB7A–positive puncta. Pacer knockout reduces Parkin mitophagy with little effect on bulk autophagy or Parkin-independent mitophagy. Rescue of Parkin-dependent mitophagy requires the intact pRAB7A phosphate-binding basic triad of Pacer. Together these structural and functional data support a model in which the TBK1-dependent phosphorylation of RAB7A serves as a switch, promoting mitophagy by relieving Rubicon inhibition and favoring Pacer activation.
... We showed before that Vps21/Rab5 both recruits and activates yeast and metazoan Mon1-Ccz1 on membranes . This process is further enhanced by the membrane environment, which the complex samples (Herrmann et al., 2023), and allows Mon1-Ccz1 to target both endosomes and autophagosomes (Gao et al., 2018;Hegedűs et al., 2016;Herrmann et al., 2023). In Drosophila and human cells, the GEF complex contains a third subunit, whose loss results in strong autophagy and endosomal defects, and lysosomal cholesterol accumulation (Vaites et al., 2017;Dehnen et al., 2020;van den Boomen et al., 2020). ...
Organelles of the endomembrane system contain Rab GTPases as identity markers. Their localization is determined by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs). It remains largely unclear how these regulators are specifically targeted to organelles and how their activity is regulated. Here, we focus on the GAP Gyp7, which acts on the Rab7-like Ypt7 protein in yeast, and surprisingly observe the protein exclusively in puncta proximal to the vacuole. Mistargeting of Gyp7 to the vacuole strongly affects vacuole morphology, suggesting that endosomal localization is needed for function. In agreement, efficient endolysosomal transport requires Gyp7. In vitro assays reveal that Gyp7 requires a distinct lipid environment for membrane binding and activity. Overexpression of Gyp7 concentrates Ypt7 in late endosomes and results in resistance to rapamycin, an inhibitor of the target of rapamycin complex 1 (TORC1), suggesting that these late endosomes are signaling endosomes. We postulate that Gyp7 is part of regulatory machinery involved in late endosome function.
... Short-term starvation treatment was performed as described in the previous study 63 . Briefly, larvae were raised at low density (25 larvae per vial). ...
Cells sense physical forces and convert them into electrical or chemical signals, a process known as mechanotransduction. Whereas extensive studies focus on mechanotransduction at the plasma membrane, little is known about whether and how intracellular organelles sense mechanical force and the physiological functions of organellar mechanosensing. Here we identify the Drosophila TMEM63 (DmTMEM63) ion channel as an intrinsic mechanosensor of the lysosome, a major degradative organelle. Endogenous DmTMEM63 proteins localize to lysosomes, mediate lysosomal mechanosensitivity and modulate lysosomal morphology and function. Tmem63 mutant flies exhibit impaired lysosomal degradation, synaptic loss, progressive motor deficits and early death, with some of these mutant phenotypes recapitulating symptoms of TMEM63-associated human diseases. Importantly, mouse TMEM63A mediates lysosomal mechanosensitivity in Neuro-2a cells, indicative of functional conservation in mammals. Our findings reveal DmTMEM63 channel function in lysosomes and its physiological roles in vivo and provide a molecular basis to explore the mechanosensitive process in subcellular organelles.
... The activity of Rab7 is intricately controlled by its GEF (GTP/GDP exchange factor) and GAP (GTPase-activating protein). A Rab7 GEF complex, Mon1-Ccz1, is directed to autophagosomes through a direct interaction with ATG8, which recruits Rab7 and HOPS to bridge autophagosomes with late endosomes/lysosomes (Gao, Langemeyer, et al., 2018;Hegedus et al., 2016). The Rab7 GAP, Armus, is recruited to autophagosomes by LC3 and aids in autophagosome maturation by regulating Rab7-GTP/Rab7-GDP cycling (Carroll et al., 2013). ...
Autophagy, a lysosome-dependent degradation process, plays a crucial role in maintaining cell homeostasis. It serves as a vital mechanism for adapting to stress and ensuring intracellular quality control. Autophagy deficiencies or defects are linked to numerous human disorders, especially those associated with neuronal degeneration or metabolic diseases. Yoshinori Ohsumi was honored with the Nobel Prize in Physiology or Medicine in 2016 for his groundbreaking discoveries regarding autophagy mechanisms. Over the past few decades, autophagy research has predominantly concentrated on the early stages of autophagy, with relatively limited attention given to the late stages. Nevertheless, recent studies have witnessed substantial advancements in understanding the molecular intricacies of the late stages, which follows autophagosome formation. This review provides a comprehensive summary of the recent progresses in comprehending the molecular mechanisms of the late stages of autophagy.
... The machinery mediating autophagosome-lysosome fusion is well characterized both in Drosophila and humans by now. Critical components include Rab2, Rab7, and Arl8 small GTPases that also contribute to de ning membrane identity 21,[26][27][28][29] , homotypic fusion and vacuole protein sorting (HOPS) tethering complex 30,31 , and a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex (SNAREpin) that executes the fusion. Based on biochemical properties, functional SNAREpins assemble from three Q-(Q abc ) and one R-SNARE domains 32 . ...
... Ykt6 is involved in the fusion of Lamp1 + vesicles with SGs Lamp1 is a highly glycosylated transmembrane protein, an essential component of the lysosomal membranes 58 . Although Lamp1 is often used as a lysosome marker, it is also present on a broader spectrum of vesicles belonging to the endo-lysosomal compartment 27,59 . Similar to our observations with Arl8, endogenous Lamp1 also forms rings along the perimeter of maturing Sgs3-dsRed SGs in control cells 2h bpf (Fig. 3e, g). ...
In the Drosophila larval salivary gland, developmentally programmed fusions between lysosomes and secretory granules (SGs) and their subsequent acidification promote the maturation of SGs that are secreted shortly before puparium formation. Subsequently, ongoing fusions between non-secreted SGs and lysosomes give rise to degradative crinosomes, where the superfluous secretory material is degraded. Lysosomal fusions control both the quality and quantity of SGs, however, its molecular mechanism is incompletely characterized. Here we identify the R-SNARE Ykt6 as a novel regulator of crinosome formation, but not the acidification of maturing SGs. We show that Ykt6 localizes to Lamp1 + carrier vesicles, and forms a SNARE complex with Syntaxin 13 and Snap29 to mediate fusion with SGs. These Lamp1 carriers represent a distinct vesicle population that are functionally different from canonical Arl8+, Cathepsin L + lysosomes, which also fuse with maturing SGs but are controlled by another SNARE complex composed of Syntaxin 13, Snap29 and Vamp7. Ykt6- and Vamp7-mediated vesicle fusions also determine the fate of SGs, as loss of either of these SNAREs prevents crinosomes from acquiring endosomal PI3P. Our results highlight that fusion events between SGs and different lysosome-related vesicle populations are critical for fine regulation of the maturation and crinophagic degradation of SGs.
... Studies have shown that Rab5 is essential for the recruitment of Rab7 to PI3Ppositive autophagosomes, and the recruitment relies on Ccz1-Mon1. Loss of Rab5 disrupts subsequent steps of autophagy (Hegedűs et al., 2016). Autophagy, a highly conserved cellular process, plays a significant role in viral infections (Chen et al., 2023;White et al., 2023). ...
Respiratory system diseases caused by respiratory viruses are common and exert tremendous pressure on global healthcare system. In our previous studies, we found that Long non-coding RNA NRAV (Lnc NRAV) and its target molecule Rab5c plays a significant role in respiratory virus infection. However, the mechanism by which Rab5c affects virus replication remains unclear. Rab5c, a protein mainly localized on the cell membranes and in early endosomes and phagosomes, participates in endocytosis mediated by clathrin and regulates the fusion of early endosome, maturation of early phagosomes, and autophagy. Therefore, we inferred that Rab5c impacts virus replication, which might be related to endocytosis or autophagy. We selected RSV (respiratory syncytial virus) as a representative enveloped virus and ADV (Adenovirus) as a representative non-enveloped virus to explore the possible mechanism of RSV and ADV replication promoted by Rab5c in A549 cells and in Rab5c-overexpressing mice. Here, we confirmed that the activated Rab5c promotes RSV and ADV replication and the inactivated Rab5c inhibits their replication. However, Rab5c promoting RSV and ADV replication is not mediated by endocytosis rather by autophagy in respiratory epithelial cells. Our study showed that Rab5c upregulates LC3-Ⅱ (microtubule-associated protein 1 light chain 3 beta) protein expression levels by interacting with Beclin1, a key autophagy molecule, which can induce autophagy and promote replication of ADV and RSV. This study enriches the understanding of the interaction between respiratory viruses and Rab5c, providing new insights for virus prevention and treatment.
... By tagging LAMPs (lysosome-associated membrane proteins participating in the transfer of molecules into and out of the lysosome) with a fluorescent marker, lysosomes can be visualized in living cells and tracked over time, which allows researchers to study the dynamics of lysosomal trafficking and the role of lysosomes in autophagy and endosomallysosomal degradation regardless of their acidification status [12,20,126]. The mCherry-Atg8a reporter is particularly effective in labeling autolysosomes because it is targeted to the autophagosome and the fluorescent signal remains stable when it is transported to the lysosome. ...
... The selective receptor of ubiquitinated proteins, commonly known as Ref (2)P/p62, is a remarkable autophagic cargo that can be tracked through fluorescent or HA-tagged reporters [20,39,130]. Not only can Ref(2)P/p62 be detected but it can also be the focus of autophagic degradation [5,131]. ...
... Not only can Ref(2)P/p62 be detected but it can also be the focus of autophagic degradation [5,131]. This means that when autophagy is functioning correctly, p62 levels are low, as it is quickly degraded; however, if autophagy is impaired, p62 accumulates and forms aggregates, and such accumulation can be visualized through the CLSM, allowing the measurement of autophagic degradation in a cell [12,20,39,132]. ...
Autophagy is the process through which a body breaks down and recycles its own cellular components, primarily inside lysosomes. It is a cellular response to starvation and stress, which plays decisive roles in various biological processes such as senescence, apoptosis, carcinoma, and immune response. Autophagy, which was first discovered as a survival mechanism during starvation in yeast, is now known to serve a wide range of functions in more advanced organisms. It plays a vital role in how cells respond to stress, starvation, and infection. While research on yeast has led to the identification of many key components of the autophagy process, more research into autophagy in more complex systems is still warranted. This review article focuses on the use of the fruit fly Drosophila melanogaster as a robust testing model in further research on autophagy. Drosophila provides an ideal environment for exploring autophagy in a living organism during its development. Additionally, Drosophila is a well-suited compact tool for genetic analysis in that it serves as an intermediate between yeast and mammals because evolution conserved the molecular machinery required for autophagy in this species. Experimental tractability of host–pathogen interactions in Drosophila also affords great convenience in modeling human diseases on analogous structures and tissues.
... A similar release is observed from yeast vacuoles (38). Furthermore, Mon1-Ccz1 is required for Rab7 activation on autophagosomes (39,40). Its targeting requires specific cues such as the recently identified amphipathic helix in Ccz1, which may recognize packaging defects within the membrane of autophagosomes (21). ...
Maturation from early to late endosomes depends on the exchange of their marker proteins Rab5 to Rab7. This requires Rab7 activation by its specific guanine nucleotide exchange factor (GEF) Mon1-Ccz1. Efficient GEF activity of this complex on membranes depends on Rab5, thus driving Rab-GTPase exchange on endosomes. However, molecular details on the role of Rab5 in Mon1-Ccz1 activation are unclear. Here, we identify key features in Mon1 involved in GEF regulation. We show that the intrinsically disordered N-terminal domain of Mon1 autoinhibits Rab5-dependent GEF activity on membranes. Consequently, Mon1 truncations result in higher GEF activity in vitro and alterations in early endosomal structures in Drosophila nephrocytes. A shift from Rab5 to more Rab7-positive structures in yeast suggests faster endosomal maturation. Using modeling, we further identify a conserved Rab5-binding site in Mon1. Mutations impairing Rab5 interaction result in poor GEF activity on membranes and growth defects in vivo. Our analysis provides a framework to understand the mechanism of Ras-related in brain (Rab) conversion and organelle maturation along the endomembrane system.
... To monitor autophagy along the dorsal trunk (DT) of L3 wandering larvae, we first used a 3×mCherry-Atg8a reporter (from now on referred to as mCh-Atg8a) that labels all autophagic structures [17,19,20]. We detected the mCh-Atg8a protein, present in the form of distinct puncta in the cytoplasm, in all cells of the DT and we quantified the number of puncta per area to identify the pattern of accumulation along the tracheal tube. ...
... Pupariation timing for all the selected individuals was scored every 2-3 h during the daytime. The [20]. The UAS-miRHG (synthetic microRNA against reaper, hid and grim, is described in [42]). ...
Polyploidy is an extended phenomenon in biology. However, its physiological significance and whether it defines specific cell behaviors is not well understood. Here we study its connection to macroautophagy/autophagy, using the larval respiratory system of Drosophila as a model. This system comprises cells with the same function yet with notably different ploidy status, namely diploid progenitors and their polyploid larval counterparts, the latter destined to die during metamorphosis. We identified an association between polyploidy and autophagy and found that higher endoreplication status correlates with elevated autophagy. Finally, we report that tissue histolysis in the trachea during Drosophila metamorphosis is mediated by autophagy, which triggers the apoptosis of polyploid cells.
... While Rab5 is normally present on early endosomes, Rab7 is predominant on LEs; this Rab5 to Rab 7 switch ensures endosome maturation (Hyttinen et al., 2013;Guerra and Bucci, 2016;Ganesan and Cai, 2021). Rab7/Ypt7 can also be recruited to autophagosomes by the Mon1-Ccz1 guanosine-exchange-factor complex in starved yeast or larval fat cells (Hegedűs et al., 2016;Gao et al., 2018). This nutrition-dependent switch in organelle localization diversifies possible functions of Rab7 but also merits caution in the interpretation of deciphering which step of autophagy may be affected. ...
Autophagy is important for cellular homeostasis and to prevent the abnormal accumulation of proteins. While many proteins that comprise the canonical autophagy pathway have been characterized, the identification of new regulators may help understand tissue and/or stress-specific responses. Using an in silico approach, we identified Striatin interacting protein (Strip), MOB kinase activator 4 (Mob4), and Fibroblast growth factor receptor 1 oncogene partner 2 (Fgop2) as conserved mediators of muscle tissue maintenance. We performed affinity purification mass spectrometry (AP-MS) experiments with Drosophila melanogaster (D. melanogaster) Strip as a bait protein and co-purified additional Striatin Interacting Phosphatase and Kinase (STRIPAK) complex members from larval muscle tissue. NUAK and Starvin (Stv) also emerged as Strip-binding proteins and these physical interactions were verified in vivo using Proximity Ligation Assays (PLA). To understand the functional significance of the STRIPAK-NUAK-Stv complex, we employed a sensitized genetic assay combined with RNA interference (RNAi) to demonstrate that both NUAK and stv function in the same biological process with genes that encode for STRIPAK complex proteins. RNAi-directed knockdown of Strip in muscle tissue led to the accumulation of ubiquitinated cargo, p62, and Atg8a, consistent with a block in autophagy. Indeed, autophagic flux was decreased in Strip RNAi muscles, while lysosome biogenesis and activity were unaffected. Our results support a model whereby the STRIPAK-NUAK-Stv complex coordinately regulates autophagy in muscle tissue.
