Transient visit of STX17 (syntaxin 17) to autophagosomes

Koyama-Honda, Ikuko; Mizushima, Noboru

doi:10.1080/15548627.2022.2079337

Cited by 4 publications

(4 citation statements)

References 12 publications

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“…, 2012 ; Tsuboyama et al. , 2016 ; Koyama-Honda and Mizushima, 2022 ). To examine the effects of WHAMM depletion on autophagosome closure, we transfected HK-2 cells with siRNAs, inhibited lysosomes with chloroquine, and stained the cells with antibodies to LC3 and STX17 ( Figure 7A ).…”

Section: Resultsmentioning

confidence: 99%

WHAMM functions in kidney reabsorption and polymerizes actin to promote autophagosomal membrane closure and cargo sequestration

Coulter,

Cortés,

Theodore

et al. 2024

MBoC

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The actin cytoskeleton is essential for many functions of eukaryotic cells, but the factors that nucleate actin assembly are not well understood at the organismal level or in the context of disease. To explore the function of the actin nucleation factor WHAMM in mice, we examined how Whamm inactivation impacts kidney physiology and cellular proteostasis. We show that male WHAMM knockout mice excrete elevated levels of albumin, glucose, phosphate, and amino acids, and display structural abnormalities of the kidney proximal tubule, suggesting that WHAMM activity is important for nutrient reabsorption. In kidney tissue, the loss of WHAMM results in the accumulation of the lipidated autophagosomal membrane protein LC3, indicating an alteration in autophagy. In mouse fibroblasts and human proximal tubule cells, WHAMM and its binding partner the Arp2/3 complex control autophagic membrane closure and cargo receptor recruitment. These results reveal a role for WHAMM-mediated actin assembly in maintaining kidney function and promoting proper autophagosome membrane remodeling.

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Section: Resultsmentioning

confidence: 99%

WHAMM functions in kidney reabsorption and polymerizes actin to promote autophagosomal membrane closure and cargo sequestration

Coulter,

Cortés,

Theodore

et al. 2024

MBoC

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“…There are many positive regulators for vesicle-vacuole fusions in the endocytosis pathway or autophagosome-vacuole fusions in autophagy, such as a yeast Ypt7 module, including GEF subunits, Mon1 and Ccz1; Rab GTPase, Ypt7; tether, HOPS complex; SNARE protein, Vam3 [9]. Previously, only closed autophagosomes were supposed to fuse with vacuoles/lysosomes to be degraded [16]. In two-dimensional topology thinking, the doublemembrane phagophores were thought to be unable to fuse with lysosomes/vacuoles to degrade enclosed cargoes.…”

Section: Discussionmentioning

confidence: 99%

“…However, these phagophores entered vacuoles under a prolonged duration of nitrogen starvation [15]. Previously, only closed autophagosomes were supposed to enter vacuoles/lysosomes [16]. However, recently, it became clear that phagophores can also fuse with lysosomes or vacuoles in mutant yeast and mammalian cells, although the molecular machinery is unknown [4,15,17].…”

Section: Introductionmentioning

confidence: 99%

Vtc4 Promotes the Entry of Phagophores into Vacuoles in the Saccharomyces cerevisiae Snf7 Mutant Cell

Chen,

Liang

2023

JoF

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Endocytosis and autophagy are the main pathways to deliver cargoes in vesicles and autophagosomes, respectively, to vacuoles/lysosomes in eukaryotes. Multiple positive regulators but few negative ones are reported to regulate the entry of vesicles and autophagosomes into vacuoles/lysosomes. In yeast, the Rab5 GTPase Vps21 and the ESCRT (endosomal sorting complex required for transport) are positive regulators in endocytosis and autophagy. During autophagy, Vps21 regulates the ESCRT to phagophores (unclosed autophagosomes) to close them. Phagophores accumulate on vacuolar membranes in both vps21∆ and ESCRT mutant cells under a short duration of nitrogen starvation. The vacuolar transport chaperon (VTC) complex proteins are recently found to be negative regulators in endocytosis and autophagy. Phagophores in vps21∆ cells are promoted to enter vacuoles when the VTC complex proteins are absent. Phagophores are easily observed inside vacuoles when any of these VTC complex proteins (Vtc1, 2, 4, 5) are removed. However, it is unknown whether the removal of VTC complex proteins will also promote the entry of phagophores into vacuoles in ESCRT mutant cells under the same conditions. Snf7 is a core subunit of ESCRT subcomplex III (ESCRT-III), and phagophores accumulate in snf7∆ cells under a short duration of nitrogen starvation. We used green fluorescence protein (GFP) labeled Atg8 to display phagophores and FM4-64-stained or Vph1-GFP-labeled membrane structures to show vacuoles, then examined fluorescence localization and GFP-Atg8 degradation in snf7∆ and snf7∆vtc4∆ cells. Results showed that Vtc4 depletion promoted the entry of phagophores in snf7∆ cells into vacuoles as it did for vps21∆ cells, although the promotion level was more obvious in vps21∆ cells. This observation indicates that the VTC complex proteins may have a widespread role in negatively regulating cargos to enter vacuoles in yeast.

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“…This can probably be attributed to a failure in lysosomes to fuse with unsealed phagophores, as ESCRT inactivation is known to cause an accumulation of "autophagosomes" (presumably representing unsealed phagophores with only a small opening) that do not progress to autolysosomes [86][87][88][89]. The SNARE protein Syntaxin-17, which mediates the autophagosome-lysosome fusion upon forming a SNARE complex with the lysosomal SNAREs SNAP29, and VAMP7/8, has been reported to associate selectively and transiently with sealed autophagosomes [90,91], and this provides a plausible explanation for the failure of unsealed phagophores to fuse with lysosomes. However, the mechanistic basis for the recruitment of Syntaxin-17 to sealed autophagosomes only has not yet been determined.…”

Section: Closure Of the Phagophorementioning

confidence: 99%

Autophagosome Biogenesis

Zhen

Stenmark

2023

Cells

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Autophagy–the lysosomal degradation of cytoplasm–plays a central role in cellular homeostasis and protects cells from potentially harmful agents that may accumulate in the cytoplasm, including pathogens, protein aggregates, and dysfunctional organelles. This process is initiated by the formation of a phagophore membrane, which wraps around a portion of cytoplasm or cargo and closes to form a double-membrane autophagosome. Upon the fusion of the autophagosome with a lysosome, the sequestered material is degraded by lysosomal hydrolases in the resulting autolysosome. Several alternative membrane sources of autophagosomes have been proposed, including the plasma membrane, endosomes, mitochondria, endoplasmic reticulum, lipid droplets, hybrid organelles, and de novo synthesis. Here, we review recent progress in our understanding of how the autophagosome is formed and highlight the proposed role of vesicles that contain the lipid scramblase ATG9 as potential seeds for phagophore biogenesis. We also discuss how the phagophore is sealed by the action of the endosomal sorting complex, which is required for transport (ESCRT) proteins.

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Transient visit of STX17 (syntaxin 17) to autophagosomes

Cited by 4 publications

References 12 publications

WHAMM functions in kidney reabsorption and polymerizes actin to promote autophagosomal membrane closure and cargo sequestration

WHAMM functions in kidney reabsorption and polymerizes actin to promote autophagosomal membrane closure and cargo sequestration

Vtc4 Promotes the Entry of Phagophores into Vacuoles in the Saccharomyces cerevisiae Snf7 Mutant Cell

Autophagosome Biogenesis

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