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https://www.readbyqxmd.com/read/28301741/mechanisms-of-autophagy-initiation
#1
James H Hurley, Lindsey N Young
Autophagy is the process of cellular self-eating by a double-membrane organelle, the autophagosome. A range of signaling processes converge on two protein complexes to initiate autophagy: the ULK1 (unc51-like autophagy activating kinase 1) protein kinase complex and the PI3KC3- C1 (class III phosphatidylinositol 3-kinase complex I) lipid kinase complex. Some 90% of the mass of these large protein complexes consists of noncatalytic domains and subunits, and the ULK1 complex has essential noncatalytic activities...
March 15, 2017: Annual Review of Biochemistry
https://www.readbyqxmd.com/read/28292851/new-insights-into-protein-secretion-tango1-runs-rings-around-the-copii-coat
#2
Benjamin S Glick
In this issue, Liu et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201611088) and Raote et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201608080) use super-resolution microscopy to visualize large COPII-coated endoplasmic reticulum (ER) export carriers. Rings of TANGO1 surround COPII, implicating TANGO1 in organizing ER exit sites and in regulating COPII coat dynamics and geometry.
March 14, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28287860/autophagosome-formation-where-the-secretory-and-autophagy-pathways-meet
#3
Juan Wang, Saralin Davis, Ming Zhu, Elizabeth A Miller, Susan Ferro-Novick
The upregulation of autophagosome formation in response to nutrient deprivation requires significant intracellular membrane rearrangements that are poorly understood. Recent findings have implicated COPII-coated vesicles, well known as ER-Golgi cargo transport carriers, as key players in macroautophagy. The role of COPII vesicles in macroautophagy and how they interact with autophagy-related (Atg) proteins was unknown. In our recent report, we show that during nutrient deprivation, phosphorylation of the membrane-distal surface of the COPII coat subunit Sec24 facilitates the interaction of Sec24 with the Atg machinery (specifically, Atg9) to regulate the abundance of autophagosomes during starvation...
February 15, 2017: Autophagy
https://www.readbyqxmd.com/read/28240221/mammalian-trappiii-complex-positively-modulates-the-recruitment-of-sec13-31-onto-copii-vesicles
#4
Shan Zhao, Chun Man Li, Xiao Min Luo, Gavin Ka Yu Siu, Wen Jia Gan, Lin Zhang, William K K Wu, Hsiao Chang Chan, Sidney Yu
The Transport protein particle (TRAPP) complex is a tethering factor for COPII vesicle. Of three forms of TRAPP (TRAPPI, II and III) complexes identified so far, TRAPPIII has been largely considered to play a role in autophagy. While depletion of TRAPPIII specific subunits caused defects in the early secretory pathway and TRAPPIII might interact with components of the COPII vesicle coat, its exact role remains to be determined. In this study, we studied the function of TRAPPIII in early secretory pathway using a TRAPPIII-specific subunit, TRAPPC12, as starting point...
February 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197529/specific-copii-vesicles-transport-er-membranes-to-sites-of-autophagosome-formation
#5
Veit Goder
The endoplasmic reticulum (ER) is considered a prominent membrane source for the formation of autophagosomes. Recent results from our laboratory revealed a cellular mechanism for the contribution of the ER to autophagosomes in yeast: membranes, together with unconventional membrane fusion machinery, are delivered to sites of autophagosome formation by specific coat protein complex II (COPII) vesicles.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28160489/sec16-in-conventional-and-unconventional-exocytosis-working-at-the-interface-of-membrane-traffic-and-secretory-autophagy
#6
REVIEW
Bor Luen Tang
Sec16 is classically perceived to be a scaffolding protein localized to the transitional endoplasmic reticulum (tER) or the ER exit sites (ERES), and has a conserved function in facilitating coat protein II (COPII) complex-mediated ER exit. Recent findings have however pointed towards a role for Sec16 in unconventional exocytosis of certain membrane proteins, such as the Cystic fibrosis transmembrane conductance regulator (CFTR) in mammalian cells, and possibly also α-integrin in certain contexts of Drosophila development...
February 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28067262/sec16a-is-critical-for-both-conventional-and-unconventional-secretion-of-cftr
#7
He Piao, Jiyoon Kim, Shin Hye Noh, Hee-Seok Kweon, Joo Young Kim, Min Goo Lee
CFTR is a transmembrane protein that reaches the cell surface via the conventional Golgi mediated secretion pathway. Interestingly, ER-to-Golgi blockade or ER stress induces alternative GRASP-mediated, Golgi-bypassing unconventional trafficking of wild-type CFTR and the disease-causing ΔF508-CFTR, which has folding and trafficking defects. Here, we show that Sec16A, the key regulator of conventional ER-to-Golgi transport, plays a critical role in the ER exit of protein cargos during unconventional secretion...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28025315/%C3%AE-2-cop-is-involved-in-early-secretory-traffic-in-arabidopsis-and-is-required-for-plant-growth
#8
Fátima Gimeno-Ferrer, Noelia Pastor-Cantizano, César Bernat-Silvestre, Pilar Selvi-Martínez, Francisco Vera-Sirera, Caiji Gao, Miguel Angel Perez-Amador, Liwen Jiang, Fernando Aniento, María Jesús Marcote
COP (coat protein) I-coated vesicles mediate intra-Golgi transport and retrograde transport from the Golgi to the endoplasmic reticulum. These vesicles form through the action of the small GTPase ADP-ribosylation factor 1 (ARF1) and the COPI heptameric protein complex (coatomer), which consists of seven subunits (α-, β-, β'-, γ-, δ-, ε- and ζ-COP). In contrast to mammals and yeast, several isoforms for coatomer subunits, with the exception of γ and δ, have been identified in Arabidopsis. To understand the role of COPI proteins in plant biology, we have identified and characterized a loss-of-function mutant of α2-COP, an Arabidopsis α-COP isoform...
December 26, 2016: Journal of Experimental Botany
https://www.readbyqxmd.com/read/27872256/the-endosomal-transcriptional-regulator-rnf11-integrates-degradation-and-transport-of-egfr
#9
Sandra Scharaw, Murat Iskar, Alessandro Ori, Gaelle Boncompain, Vibor Laketa, Ina Poser, Emma Lundberg, Franck Perez, Martin Beck, Peer Bork, Rainer Pepperkok
Stimulation of cells with epidermal growth factor (EGF) induces internalization and partial degradation of the EGF receptor (EGFR) by the endo-lysosomal pathway. For continuous cell functioning, EGFR plasma membrane levels are maintained by transporting newly synthesized EGFRs to the cell surface. The regulation of this process is largely unknown. In this study, we find that EGF stimulation specifically increases the transport efficiency of newly synthesized EGFRs from the endoplasmic reticulum to the plasma membrane...
November 21, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27872251/regulation-of-egfr-surface-levels-by-copii-dependent-trafficking
#10
Hesso Farhan
Cell surface levels of epidermal growth factor receptors (EGFRs) are thought to be controlled mainly by endocytic trafficking, with biosynthetic EGFR trafficking presumed to be a constitutive and unregulated process. However, Scharaw et al. (2016. J. Cell Biol http://dx.doi.org/10.1083/jcb.201601090) demonstrate a role for inducible COPII trafficking in controlling EGFR surface levels.
November 21, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27856517/mglur-long-term-depression-regulates-glua2-association-with-copii-vesicles-and-exit-from-the-endoplasmic-reticulum
#11
Joseph E Pick, Latika Khatri, Matheus F Sathler, Edward B Ziff
mGluR long-term depression (mGluR-LTD) is a form of synaptic plasticity induced at excitatory synapses by metabotropic glutamate receptors (mGluRs). mGluR-LTD reduces synaptic strength and is relevant to learning and memory, autism, and sensitization to cocaine; however, the mechanism is not known. Here we show that activation of Group I mGluRs in medium spiny neurons induces trafficking of GluA2 from the endoplasmic reticulum (ER) to the synapse by enhancing GluA2 binding to essential COPII vesicle proteins, Sec23 and Sec13...
January 17, 2017: EMBO Journal
https://www.readbyqxmd.com/read/27855785/sec24-phosphorylation-regulates-autophagosome-abundance-during-nutrient-deprivation
#12
Saralin Davis, Juan Wang, Ming Zhu, Kyle Stahmer, Ramya Lakshminarayan, Majid Ghassemian, Yu Jiang, Elizabeth A Miller, Susan Ferro-Novick
Endoplasmic Reticulum (ER)-derived COPII coated vesicles constitutively transport secretory cargo to the Golgi. However, during starvation-induced stress, COPII vesicles have been implicated as a membrane source for autophagosomes, distinct organelles that engulf cellular components for degradation by macroautophagy (hereafter called autophagy). How cells regulate core trafficking machinery to fulfill dramatically different cellular roles in response to environmental cues is unknown. Here we show that phosphorylation of conserved amino acids on the membrane-distal surface of the Saccharomyces cerevisiae COPII cargo adaptor, Sec24, reprograms COPII vesicles for autophagy...
November 18, 2016: ELife
https://www.readbyqxmd.com/read/27813252/the-calcium-binding-protein-alg-2-promotes-endoplasmic-reticulum-exit-site-localization-and-polymerization-of-trk-fused-gene-tfg-protein
#13
Takashi Kanadome, Hideki Shibata, Keiko Kuwata, Terunao Takahara, Masatoshi Maki
Apoptosis-linked gene 2 (ALG-2), which is a gene product of PDCD6, is a 22-kDa Ca(2+) -binding protein. Accumulating evidence points to a role for ALG-2 as a Ca(2+) -responsive adaptor protein. On binding to Ca(2+) , ALG-2 undergoes a conformational change that facilitates its interaction with various proteins. It also forms a homodimer and heterodimer with peflin, a paralog of ALG-2. However, the differences in cellular roles for the ALG-2 homodimer and ALG-2/peflin heterodimer are unclear. In the present study, we found that Trk-fused gene (TFG) protein interacted with the ALG-2 homodimer...
November 4, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27803308/golgi-transport-1b-regulates-protein-export-from-the-endoplasmic-reticulum-in-rice-endosperm-cells
#14
Yihua Wang, Feng Liu, Yulong Ren, Yunlong Wang, Xi Liu, Wuhua Long, Di Wang, Jianping Zhu, Xiaopin Zhu, Ruonan Jing, Mingming Wu, Yuanyuan Hao, Ling Jiang, Chunming Wang, Haiyang Wang, Yiqun Bao, Jianmin Wan
Coat protein complex II (COPII) mediates the first step of anterograde transport of newly synthesized proteins from the endoplasmic reticulum (ER) to other endomembrane compartments in eukaryotes. A group of evolutionarily conserved proteins (Sar1, Sec23, Sec24, Sec13, and Sec31) constitutes the basic COPII coat machinery; however, the details of how the COPII coat assembly is regulated remain unclear. Here, we report a protein transport mutant of rice (Oryza sativa), named glutelin precursor accumulation4 (gpa4), which accumulates 57-kD glutelin precursors and forms two types of ER-derived abnormal structures...
November 2016: Plant Cell
https://www.readbyqxmd.com/read/27802842/defective-anks1a-disrupts-the-export-of-receptor-tyrosine-kinases-from-the-endoplasmic-reticulum
#15
Soochul Park
EphA2 has been implicated in amplifying ErbB2 tumorigenic signaling. One protein that interacts with EphA2 is the Anks1a PTB adaptor. However, the precise role of Anks1a in EphA2-mediated tumorigenesis is unclear. We demonstrated that Anks1a localizes to the ER upon phosphorylation and that the Ankyrin repeats and PTB of Anks1a bind to EphA2 and Sec23, respectively. Thus, Anks1a facilitates the selective packaging of EphA2 into COPII vesicles. Additionally, Anks1a knockout mice, a phenocopy of EphA2 knockout mice, exhibited markedly reduced ErbB2-induced breast tumorigenesis...
December 2016: BMB Reports
https://www.readbyqxmd.com/read/27716508/regulation-of-the-cul3%C3%A2-ubiquitin-ligase-by-a-calcium-dependent-co-adaptor
#16
Colleen A McGourty, David Akopian, Carolyn Walsh, Amita Gorur, Achim Werner, Randy Schekman, Diana Bautista, Michael Rape
The ubiquitin ligase CUL3 is an essential regulator of neural crest specification whose aberrant activation has been linked to autism, schizophrenia, and hypertension. CUL3 exerts its roles by pairing with ∼90 distinct substrate adaptors, yet how the different CUL3-complexes are activated is poorly understood. Here, we show that CUL3 and its adaptor KLHL12 require two calcium-binding proteins, PEF1 and ALG2, for recognition of their substrate SEC31. PEF1 and ALG2 form a target-specific co-adaptor that translates a transient rise in cytosolic calcium levels into more persistent SEC31 ubiquitylation, which in turn triggers formation of large COPII coats and promotes collagen secretion...
October 6, 2016: Cell
https://www.readbyqxmd.com/read/27679847/intracellular-mechanisms-of-molecular-recognition-and-sorting-for-transport-of-large-extracellular-matrix-molecules
#17
Yoshihiro Ishikawa, Shinya Ito, Kazuhiro Nagata, Lynn Y Sakai, Hans Peter Bächinger
Extracellular matrix (ECM) proteins are biosynthesized in the rough endoplasmic reticulum (rER) and transported via the Golgi apparatus to the extracellular space. The coat protein complex II (COPII) transport vesicles are approximately 60-90 nm in diameter. However, several ECM molecules are much larger, up to several hundreds of nanometers. Therefore, special COPII vesicles are required to coat and transport these molecules. Transmembrane Protein Transport and Golgi Organization 1 (TANGO1) facilitates loading of collagens into special vesicles...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27634427/secretory-copii-protein-sec31b-is-required-for-pollen-wall-development
#18
Bing-Chun Zhao, Hai-Dan Shi, Wan-Lei Wang, Xiao-Yu Liu, Hui Gao, Xiao-Xiao Wang, Ying Hui Zhang, Mei Di Yang, Rui Li, Yi Guo
The pollen wall protects pollen grains from abiotic and biotic stresses. During pollen wall development, tapetal cells play vital role by secreting proteins, signals and pollen wall material to ensure microspore development. But the regulatory mechanism underlying the secretory pathway of the tapetum is largely unknown. Here, we characterize the essential role of the Arabidopsis COPII protein Secretory31B (SEC31B) in pollen wall development and secretive activity of tapetal cells. The sporophyte-controlled atsec31b mutant exhibits severe pollen and seed abortion...
September 15, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27619642/anks1a-regulates-copii-mediated-anterograde-transport-of-receptor-tyrosine-kinases-critical-for-tumorigenesis
#19
Haeryung Lee, Hyuna Noh, Jiyoung Mun, Changkyu Gu, Sanja Sever, Soochul Park
ErbB2 signalling, which is amplified by EphA2 binding, is an important therapeutic target for breast cancer. Despite the importance of the EphA2/ErbB2 complex in promoting breast tumorigenesis, the mechanism by which these receptor tyrosine kinases (RTKs) are exported from the endoplasmic reticulum (ER) remains poorly understood. Here we report that the PTB adaptor Anks1a is specifically localized to the ER on its own serine phosphorylation. Once there, Anks1a acts as an important regulator of COPII-mediated EphA2 ER export...
2016: Nature Communications
https://www.readbyqxmd.com/read/27590193/three-dimensional-and-immune-electron-microscopic-analysis-of-the-secretory-pathway-in-saccharomyces-cerevisiae
#20
Galina V Beznoussenko, Antonella Ragnini-Wilson, Cathal Wilson, Alexander A Mironov
Until now, the mechanisms of ER-to-Golgi and intra-Golgi transport remain obscure. This is especially evident for the Golgi of S. cerevisiae where different Golgi compartments are not organized in stacks. Here, using improved sample preparation protocols, we examined the 3D organization of pre-Golgi and Golgi compartments and found several new features of the structures functioning along the secretory pathway. In the cytoplasmic sheet ER, we found narrow pores that aggregated near the rims, and tubular networks tightly interconnected with sheets of several cytoplasmic ER cisternae...
November 2016: Histochemistry and Cell Biology
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