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author:("Xie, shipping")
1.  A Vps21 endocytic module regulates autophagy 
Molecular Biology of the Cell  2014;25(20):3166-3177.
Vps21 plays a role in autophagy in addition to its role in endocytosis. Individual deletions of members of the endocytic Vps21 module, including a GEF and four effectors, result in autophagy defects and accumulation of autophagosomal clusters. Therefore the endocytic Vps21 module regulates autophagy.
In autophagy, the double-membrane autophagosome delivers cellular components for their degradation in the lysosome. The conserved Ypt/Rab GTPases regulate all cellular trafficking pathways, including autophagy. These GTPases function in modules that include guanine-nucleotide exchange factor (GEF) activators and downstream effectors. Rab7 and its yeast homologue, Ypt7, in the context of such a module, regulate the fusion of both late endosomes and autophagosomes with the lysosome. In yeast, the Rab5-related Vps21 is known for its role in early- to late-endosome transport. Here we show an additional role for Vps21 in autophagy. First, vps21∆ mutant cells are defective in selective and nonselective autophagy. Second, fluorescence and electron microscopy analyses show that vps21∆ mutant cells accumulate clusters of autophagosomal structures outside the vacuole. Third, cells with mutations in other members of the endocytic Vps21 module, including the GEF Vps9 and factors that function downstream of Vps21, Vac1, CORVET, Pep12, and Vps45, are also defective in autophagy and accumulate clusters of autophagosomes. Finally, Vps21 localizes to PAS. We propose that the endocytic Vps21 module also regulates autophagy. These findings support the idea that the two pathways leading to the lysosome—endocytosis and autophagy—converge through the Vps21 and Ypt7 GTPase modules.
doi:10.1091/mbc.E14-04-0917
PMCID: PMC4196867  PMID: 25143401
2.  Sleep-Related Factors and Work-Related Injuries among Farmers in Heilongjiang Province, People’s Republic of China 
The association between sleep and work-related injuries among Chinese farmers has not been well studied. This study examined the impact of lack of sleep on agricultural work-related injuries among farmers in China. Data were from a cross-sectional survey of farm-workers in northeastern China. Information was obtained on injuries that occurred in 12 months prior to the survey, on eight sleep-related variables, and on socio-demographic variables. Logistic regression analyses were conducted to test the hypothesis that lack of sleep significantly increased the risk of work-related injuries after controlling for other injury-related risk- factors. Farmers who slept less than six hours per night were 59% more likely to be injured than those who slept more than eight hours per night (OR = 1.59; 95% CI = 1.04, 2.41). The odds of a work-related injury was 2.46 (1.56–3.89) for farmers who reported going to sleep after midnight at least once a week compared with farmers who reported going to sleep after midnight once a month. Farmers who reported having difficulty falling asleep or waking frequently during the night, who often having nightmares, or who experienced daytime sleepiness were at higher injury risk compared with the reference group after controlling for age, gender and alcohol consumption. Reduced sleep hours and poor sleep quality significantly increased the risk of work-related injuries in Chinese farmers. Sleep hours and sleep quality should be considered when assessing occupational safety among farmers.
doi:10.3390/ijerph110909446
PMCID: PMC4199028  PMID: 25216255
sleep-related factors; injury; agriculture; association; Chinese farmers
3.  Trs130 participates in autophagy through GTPases Ypt31/32 in Saccharomyces cerevisiae 
Traffic (Copenhagen, Denmark)  2012;14(2):233-246.
Trs130 is a specific component of the TRAPP II (Transport protein particle II) complex, which functions as a guanine exchange factor (GEF) for Rab GTPases Ypt31/32. Ypt31/32 is known to be involved in autophagy, although the precise mechanism has not been thoroughly studied. In this study, we investigated the potential involvement of Trs130 in autophagy and found that both the cytoplasm-to-vacuole targeting (Cvt) pathway and starvation-induced autophagy were defective in a trs130ts (trs130 temperature-sensitive) mutant. Mutant cells could not transport Atg8 and Atg9 to the preautophagosomal structure/ phagophore assembly site (PAS) properly, resulting in multiple Atg8 dots and Atg9 dots dispersed in the cytoplasm. Some dots were trapped in the trans-Golgi. Genetic studies showed that the effect of the Trs130 mutation was downstream of Atg5 and upstream of Atg1, Atg13, Atg9 and Atg14 on the autophagic pathway. Furthermore, overexpression of Ypt31 or Ypt32, but not of Ypt1, rescued autophagy defects in trs130ts and trs65ts (Trs130-HA Trs120-myc trs65Δ) mutants. Our data provide mechanistic insight into how Trs130 participates in autophagy and suggest that vesicular trafficking regulated by GTPases/GEFs is important in the transport of autophagy proteins from the trans-Golgi to the PAS.
doi:10.1111/tra.12024
PMCID: PMC3538905  PMID: 23078654
TRAPP II; GEF complex; Ypt31/32; Rab GTPases; autophagy
4.  A role for Atg8–PE deconjugation in autophagosome biogenesis 
Autophagy  2012;8(5):780-793.
Formation of the autophagosome is likely the most complex step of macroautophagy, and indeed it is the morphological and functional hallmark of this process; accordingly, it is critical to understand the corresponding molecular mechanism. Atg8 is the only known autophagy-related (Atg) protein required for autophagosome formation that remains associated with the completed sequestering vesicle. Approximately one-fourth of all of the characterized Atg proteins that participate in autophagosome biogenesis affect Atg8, regulating its conjugation to phosphatidylethanolamine (PE), localization to the phagophore assembly site and/or subsequent deconjugation. An unanswered question in the field regards the physiological role of the deconjugation of Atg8–PE. Using an Atg8 mutant that bypasses the initial Atg4-dependent processing, we demonstrate that Atg8 deconjugation is an important step required to facilitate multiple events during macroautophagy. The inability to deconjugate Atg8–PE results in the mislocalization of this protein to the vacuolar membrane. We also show that the deconjugation of Atg8–PE is required for efficient autophagosome biogenesis, the assembly of Atg9-containing tubulovesicular clusters into phagophores/autophagosomes, and for the disassembly of PAS-associated Atg components.
doi:10.4161/auto.19385
PMCID: PMC3378420  PMID: 22622160
5.  Dual roles of Atg8−PE deconjugation by Atg4 in autophagy 
Autophagy  2012;8(6):883-892.
Modification of target molecules by ubiquitin or ubiquitin-like (Ubl) proteins is generally reversible. Little is known, however, about the physiological function of the reverse reaction, deconjugation. Atg8 is a unique Ubl protein whose conjugation target is the lipid phosphatidylethanolamine (PE). Atg8 functions in the formation of double-membrane autophagosomes, a central step in the well-conserved intracellular degradation pathway of macroautophagy (hereafter autophagy). Here we show that the deconjugation of Atg8−PE by the cysteine protease Atg4 plays dual roles in the formation of autophagosomes. During the early stage of autophagosome formation, deconjugation releases Atg8 from non-autophagosomal membranes to maintain a proper supply of Atg8. At a later stage, the release of Atg8 from intermediate autophagosomal membranes facilitates the maturation of these structures into fusion-capable autophagosomes. These results provide new insights into the functions of Atg8−PE and its deconjugation.
doi:10.4161/auto.19652
PMCID: PMC3427254  PMID: 22652539
autophagy; ubiquitin-like proteins; deconjugation; Atg4; Atg8
6.  Indirect estimation of the area density of Atg8 on the phagophore 
Autophagy  2009;5(2):217-220.
Atg8 is a ubiquitin-like protein that controls the expansion of the phagophore during autophagosome formation. It is recruited to the phagophore during the expansion stage and released upon the completion of the autophagosome. One possible model explaining the function of Atg8 is that it acts as an adaptor of a coat complex. Here, we tested the coat-adaptor model by estimating the area density of Atg8 molecules on the phagophore. We developed a computational process to simulate the random sectioning of vesicles heterogeneous in size. This method can be applied to estimate the original sizes of intracellular vesicles from sizes of their random sections obtained through transmission electron microscopy. Using this method, we found that the estimated area density of Atg8 is comparable with that of proteins that form the COPII coat.
PMCID: PMC2941343  PMID: 19088501
Autophagy; lysosome; stress; vacuole; yeast
7.  Atg8 Controls Phagophore Expansion during Autophagosome Formation 
Molecular Biology of the Cell  2008;19(8):3290-3298.
Autophagy is a potent intracellular degradation process with pivotal roles in health and disease. Atg8, a lipid-conjugated ubiquitin-like protein, is required for the formation of autophagosomes, double-membrane vesicles responsible for the delivery of cytoplasmic material to lysosomes. How and when Atg8 functions in this process, however, is not clear. Here we show that Atg8 controls the expansion of the autophagosome precursor, the phagophore, and give the first real-time, observation-based temporal dissection of the autophagosome formation process. We demonstrate that the amount of Atg8 determines the size of autophagosomes. During autophagosome biogenesis, Atg8 forms an expanding structure and later dissociates from the site of vesicle formation. On the basis of the dynamics of Atg8, we present a multistage model of autophagosome formation. This model provides a foundation for future analyses of the functions and dynamics of known autophagy-related proteins and for screening new genes.
doi:10.1091/mbc.E07-12-1292
PMCID: PMC2488302  PMID: 18508918

Results 1-7 (7)