The growth of Caenorhabditis elegans involves multiple molting processes,during which old cuticles are shed and new cuticles are rapidly formed.This process requires the regulated bulk secretion of cuticle components....The growth of Caenorhabditis elegans involves multiple molting processes,during which old cuticles are shed and new cuticles are rapidly formed.This process requires the regulated bulk secretion of cuticle components.The transmembrane protein-39(TMEM-39)mutant exhibits distinct dumpy and ruptured phenotypes characterized by notably thin cuticles.TMEM-39 primarily co-localizes with the coat protein II complex(COPII)in large vesicles rather than small COPII vesicles.These TMEM-39-associated large vesicles(TMEM-39-LVs)form robustly during the molting period and co-localize with various extracellular matrix components,including BLI-1 collagen,BLI-3 dual oxidase,and carboxypeptidases.Through immunoprecipitation using TMEM39A-FLAG and proteomics analysis in human sarcoma cells,we identify TMEM39A-associated proteins,including TMEM131.Knockdown of TMEM131 results in reduced TMEM39A-LV formation and collagen secretion in both C.elegans and human sarcoma cells,indicating a cooperative role between TMEM39A and TMEM131 in the secretion of extracellular components through the formation of large COPII vesicles.Given the conservation of TMEM39A and its associated proteins between C.elegans and humans,TMEM39A-LVs may represent a fundamental machinery for rapid and extensive secretion across metazoans.展开更多
The endoplasmic reticulum(ER)is the site of entry of all proteins that function in the secretory pathway including the extracellular environment.Because it controls the folding of newly synthesized secretory proteins,...The endoplasmic reticulum(ER)is the site of entry of all proteins that function in the secretory pathway including the extracellular environment.Because it controls the folding of newly synthesized secretory proteins,the ER is indispensable for the maintenance of proteostasis in the secretory pathway.Within the ER and,in part,in post-ER compartments,the quality control of protein folding is under the regulation of the unfolded protein response(UPR)pathways.The UPR strategy is to enhance protein folding,increase the ER degradation pathway of misfolded proteins,and allow the exit from the ER of only correctly folded proteins.The latter is controlled by the multimeric complex COPII,which also provides some of the components for ER-phagy the only route for the disposal of protein aggregates.In this overview,we wish to contribute to the introduction of new perspectives in the study of the mechanisms underlying the control of proteostasis within the secretory pathway.展开更多
HSF-1 is a highly conserved transcription factor that plays a central role in protecting organisms from diverse cellular stresses.However,the mechanisms by which HSF-1 senses and responds to different types of stress ...HSF-1 is a highly conserved transcription factor that plays a central role in protecting organisms from diverse cellular stresses.However,the mechanisms by which HSF-1 senses and responds to different types of stress remain incompletely understood.COPIIcoated vesicles,responsible for transporting cargo from the endoplasmic reticulum to the Golgi apparatus,are essential for protein secretion and cellular homeostasis.Disruption of these vesicles impairs protein secretion and triggers severe proteotoxic stress.Here,we show that HSF-1 directly monitors COPII vesicle dysfunction through interactions with the core COPII component SEC-23,in both Caenorhabditis elegans and NIH3T3 cells.Inhibition of SEC-23 or SAR-1 disrupts COPII vesicle formation,leading to the release of HSF-1 from the COPII complex.This release induces a specific transcriptomic change to restore protein homeostasis.Our findings reveal a conserved mechanism by which HSF-1 responds to COPII vesicle dysregulation,providing new insights into the HSF-1-centered proteostasis network.展开更多
在真核细胞中,囊泡介导的蛋白质转运是一个高度可控的多步骤过程。在囊泡与靶细胞器膜成分融合之前,许多因子参与了它们之间的特异性识别和拴系。其中大部分由多亚基复合体或卷曲螺旋蛋白构成的拴系因子,在小G蛋白的协助下,介导了囊泡...在真核细胞中,囊泡介导的蛋白质转运是一个高度可控的多步骤过程。在囊泡与靶细胞器膜成分融合之前,许多因子参与了它们之间的特异性识别和拴系。其中大部分由多亚基复合体或卷曲螺旋蛋白构成的拴系因子,在小G蛋白的协助下,介导了囊泡与靶细胞器膜成分之间最初的结合。转运蛋白颗粒(transport protein particle,TRAPP)复合体就是一种广泛参与囊泡在细胞内转运的多亚基拴系因子。本文将就TRAPP复合体结构与功能的最新研究进展及与TRAPP复合体基因突变相关疾病做一简单综述和总结。展开更多
Introduction Macroautophagy(hereafter referred as autophagy)is a process of cellular self-degradation.In response to nutrient deprivation or other stimuli,a nascent double-membrane autophagosome,encapsulating intracel...Introduction Macroautophagy(hereafter referred as autophagy)is a process of cellular self-degradation.In response to nutrient deprivation or other stimuli,a nascent double-membrane autophagosome,encapsulating intracellular materials or damaged organelles,is generated.The autophagosome is transported toward and eventually fuses with the lysosome(or the vacuole in yeast and plant cells).展开更多
Coat protein complex Ⅱ(COPⅡ)-coated vesicles are responsible for transporting the cargoes from the endoplasmic reticulum(ER) to different destinations. c TAGE5/MEA6 is essential for the development and function of d...Coat protein complex Ⅱ(COPⅡ)-coated vesicles are responsible for transporting the cargoes from the endoplasmic reticulum(ER) to different destinations. c TAGE5/MEA6 is essential for the development and function of different organs. It regulates the assembly of COPⅡ carrier and cargo trafficking through direct or indirect interaction with COPII components. c TAGE5/MEA6 mainly coordinates with another scaffold protein, TANGO1, to play essential roles in the trafficking and secretion of both large and small cargoes in multiple organs. In this viewpoint, we would like to discuss the molecular mechanisms underlying c TAGE5/MEA6-mediated cargo transport and biological functions.展开更多
基金supported by the National Institutes of Health-Office of Research Infrastructure Programs(P40 OD010440)supported in part by grants from the National Cancer Center of Korea(NCC-2110160,NCC-2110263,and NCC-2310750)supported by the Basic Science Research Program of the National Research Foundation of Korea,funded by the Ministry of Science,ICT,and Future Planning(NRF-2015R1C1A1A01053611).
文摘The growth of Caenorhabditis elegans involves multiple molting processes,during which old cuticles are shed and new cuticles are rapidly formed.This process requires the regulated bulk secretion of cuticle components.The transmembrane protein-39(TMEM-39)mutant exhibits distinct dumpy and ruptured phenotypes characterized by notably thin cuticles.TMEM-39 primarily co-localizes with the coat protein II complex(COPII)in large vesicles rather than small COPII vesicles.These TMEM-39-associated large vesicles(TMEM-39-LVs)form robustly during the molting period and co-localize with various extracellular matrix components,including BLI-1 collagen,BLI-3 dual oxidase,and carboxypeptidases.Through immunoprecipitation using TMEM39A-FLAG and proteomics analysis in human sarcoma cells,we identify TMEM39A-associated proteins,including TMEM131.Knockdown of TMEM131 results in reduced TMEM39A-LV formation and collagen secretion in both C.elegans and human sarcoma cells,indicating a cooperative role between TMEM39A and TMEM131 in the secretion of extracellular components through the formation of large COPII vesicles.Given the conservation of TMEM39A and its associated proteins between C.elegans and humans,TMEM39A-LVs may represent a fundamental machinery for rapid and extensive secretion across metazoans.
基金This work was supported by POR FERS Regione Campania 2014–2020 ASSE 1 O.S 1.2grant System Innovation for Cancer Early Diagnosis(SICED).
文摘The endoplasmic reticulum(ER)is the site of entry of all proteins that function in the secretory pathway including the extracellular environment.Because it controls the folding of newly synthesized secretory proteins,the ER is indispensable for the maintenance of proteostasis in the secretory pathway.Within the ER and,in part,in post-ER compartments,the quality control of protein folding is under the regulation of the unfolded protein response(UPR)pathways.The UPR strategy is to enhance protein folding,increase the ER degradation pathway of misfolded proteins,and allow the exit from the ER of only correctly folded proteins.The latter is controlled by the multimeric complex COPII,which also provides some of the components for ER-phagy the only route for the disposal of protein aggregates.In this overview,we wish to contribute to the introduction of new perspectives in the study of the mechanisms underlying the control of proteostasis within the secretory pathway.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19000000)。
文摘HSF-1 is a highly conserved transcription factor that plays a central role in protecting organisms from diverse cellular stresses.However,the mechanisms by which HSF-1 senses and responds to different types of stress remain incompletely understood.COPIIcoated vesicles,responsible for transporting cargo from the endoplasmic reticulum to the Golgi apparatus,are essential for protein secretion and cellular homeostasis.Disruption of these vesicles impairs protein secretion and triggers severe proteotoxic stress.Here,we show that HSF-1 directly monitors COPII vesicle dysfunction through interactions with the core COPII component SEC-23,in both Caenorhabditis elegans and NIH3T3 cells.Inhibition of SEC-23 or SAR-1 disrupts COPII vesicle formation,leading to the release of HSF-1 from the COPII complex.This release induces a specific transcriptomic change to restore protein homeostasis.Our findings reveal a conserved mechanism by which HSF-1 responds to COPII vesicle dysregulation,providing new insights into the HSF-1-centered proteostasis network.
文摘在真核细胞中,囊泡介导的蛋白质转运是一个高度可控的多步骤过程。在囊泡与靶细胞器膜成分融合之前,许多因子参与了它们之间的特异性识别和拴系。其中大部分由多亚基复合体或卷曲螺旋蛋白构成的拴系因子,在小G蛋白的协助下,介导了囊泡与靶细胞器膜成分之间最初的结合。转运蛋白颗粒(transport protein particle,TRAPP)复合体就是一种广泛参与囊泡在细胞内转运的多亚基拴系因子。本文将就TRAPP复合体结构与功能的最新研究进展及与TRAPP复合体基因突变相关疾病做一简单综述和总结。
基金funded by Beijing Natural Science Foundation(JQ20028)the National Natural Science Foundation of China(32130023,91854114,32061143009)Ministry of Science and Technology of the People’s Republic of China(2019YFA0508602,2021YFA0804802)。
文摘Introduction Macroautophagy(hereafter referred as autophagy)is a process of cellular self-degradation.In response to nutrient deprivation or other stimuli,a nascent double-membrane autophagosome,encapsulating intracellular materials or damaged organelles,is generated.The autophagosome is transported toward and eventually fuses with the lysosome(or the vacuole in yeast and plant cells).
基金supported by grants from the National Natural Science Foundation of China(91854118,31921002,31730108,32061143026)the major projects of the Ministry of Science and Technology(2021ZD0202300)Chinese Academy of Sciences(XDB32020100,YJKYYQ20200052)。
文摘Coat protein complex Ⅱ(COPⅡ)-coated vesicles are responsible for transporting the cargoes from the endoplasmic reticulum(ER) to different destinations. c TAGE5/MEA6 is essential for the development and function of different organs. It regulates the assembly of COPⅡ carrier and cargo trafficking through direct or indirect interaction with COPII components. c TAGE5/MEA6 mainly coordinates with another scaffold protein, TANGO1, to play essential roles in the trafficking and secretion of both large and small cargoes in multiple organs. In this viewpoint, we would like to discuss the molecular mechanisms underlying c TAGE5/MEA6-mediated cargo transport and biological functions.
