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https://www.readbyqxmd.com/read/27872256/the-endosomal-transcriptional-regulator-rnf11-integrates-degradation-and-transport-of-egfr
#1
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
#2
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
#3
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...
November 17, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27855785/sec24-phosphorylation-regulates-autophagosome-abundance-during-nutrient-deprivation
#4
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-er-exit-site-localization-and-polymerization-of-tfg
#5
Takashi Kanadome, Hideki Shibata, Keiko Kuwata, Terunao Takahara, Masatoshi Maki
ALG-2 (apoptosis-linked gene 2, 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. Here, we found that TFG (Trk-fused gene) interacted with the ALG-2 homodimer...
November 4, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27803308/golgi-transport-1b-regulates-protein-export-from-endoplasmic-reticulum-in-rice-endosperm-cells
#6
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-kDa glutelin precursors, and forms two types of ER-derived abnormal structures...
November 1, 2016: Plant Cell
https://www.readbyqxmd.com/read/27802842/defective-anks1a-disrupts-the-export-of-receptor-tyrosine-kinases-from-the-endoplasmic-reticulum
#7
Soochul Park
EphA2 has been implicated in amplifying ErbB2 tumorigenic signaling. One protein that interacts with EphA2 is 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 knock-out mice, a phenocopy of EphA2 knock-out mice, exhibited markedly reduced ErbB2-induced breast tumorigenesis...
November 2, 2016: BMB Reports
https://www.readbyqxmd.com/read/27716508/regulation-of-the-cul3%C3%A2-ubiquitin-ligase-by-a-calcium-dependent-co-adaptor
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/27587840/inhibition-of-cargo-export-at-er-exit-sites-and-the-trans-golgi-network-by-the-secretion-inhibitor-fli-06
#13
Yoji Yonemura, Xiaolin Li, Katja Müller, Andreas Krämer, Paul Atigbire, Torben Mentrup, Talitha Feuerhake, Torsten Kroll, Olga Shomron, Richard Nohl, Hans-Dieter Arndt, Christian Hoischen, Peter Hemmerich, Koret Hirschberg, Christoph Kaether
Export out of the endoplasmic reticulum (ER) involves the Sar1 and COPII machinery acting at ER exit sites (ERES). Whether and how cargo proteins are recruited upstream of Sar1 and COPII is unclear. Two models are conceivable, a recruitment model where cargo is actively transported through a transport factor and handed over to the Sar1 and COPII machinery in ERES, and a capture model, where cargo freely diffuses into ERES where it is captured by the Sar1 and COPII machinery. Using the novel secretion inhibitor FLI-06, we show that recruitment of the cargo VSVG to ERES is an active process upstream of Sar1 and COPII...
October 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27571067/multifaceted-roles-of-alg-2-in-ca-2-regulated-membrane-trafficking
#14
REVIEW
Masatoshi Maki, Terunao Takahara, Hideki Shibata
ALG-2 (gene name: PDCD6) is a penta-EF-hand Ca(2+)-binding protein and interacts with a variety of proteins in a Ca(2+)-dependent fashion. ALG-2 recognizes different types of identified motifs in Pro-rich regions by using different hydrophobic pockets, but other unknown modes of binding are also used for non-Pro-rich proteins. Most ALG-2-interacting proteins associate directly or indirectly with the plasma membrane or organelle membranes involving the endosomal sorting complex required for transport (ESCRT) system, coat protein complex II (COPII)-dependent ER-to-Golgi vesicular transport, and signal transduction from membrane receptors to downstream players...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27555326/pharmacological-chaperones-of-the-dopamine-transporter-rescue-dopamine-transporter-deficiency-syndrome-mutations-in-heterologous-cells
#15
Pieter Beerepoot, Vincent M Lam, Ali Salahpour
A number of pathological conditions have been linked to mutations in the dopamine transporter gene, including hereditary dopamine transporter deficiency syndrome (DTDS). DTDS is a rare condition that is caused by autosomal recessive loss-of-function mutations in the dopamine transporter (DAT), which often affects transporter trafficking and folding. We examined the possibility of using pharmacological chaperones of DAT to rescue DTDS mutations. After screening a set of known DAT ligands for their ability to increase DAT surface expression, we found that bupropion and ibogaine increased DAT surface expression, whereas others, including cocaine and methylphenidate, had no effect...
October 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27551091/tango1-ctage5-receptor-as-a-polyvalent-template-for-assembly-of-large-copii-coats
#16
Wenfu Ma, Jonathan Goldberg
The supramolecular cargo procollagen is loaded into coat protein complex II (COPII)-coated carriers at endoplasmic reticulum (ER) exit sites by the receptor molecule TANGO1/cTAGE5. Electron microscopy studies have identified a tubular carrier of suitable dimensions that is molded by a distinctive helical array of the COPII inner coat protein Sec23/24•Sar1; the helical arrangement is absent from canonical COPII-coated small vesicles. In this study, we combined X-ray crystallographic and biochemical analysis to characterize the association of TANGO1/cTAGE5 with COPII proteins...
September 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27539921/an-unrecognized-function-for-copii-components-in-recruiting-the-viral-replication-protein-bmv-1a-to-the-perinuclear-er
#17
Jianhui Li, Shai Fuchs, Jiantao Zhang, Sebastian Wellford, Maya Schuldiner, Xiaofeng Wang
Positive-strand RNA viruses invariably assemble their viral replication complexes (VRCs) by remodeling host intracellular membranes. How viral replication proteins are targeted to specific organelle membranes to initiate VRC assembly remains elusive. Brome mosaic virus (BMV), whose replication can be recapitulated in Saccharomyces cerevisiae, assembles its VRCs by invaginating the outer perinuclear endoplasmic reticulum (ER) membrane. Remarkably, BMV replication protein 1a (BMV 1a) is the only viral protein required for such membrane remodeling...
October 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27507854/crebh-couples-circadian-clock-with-hepatic-lipid-metabolism
#18
Ze Zheng, Hyunbae Kim, Yining Qiu, Xuequn Chen, Roberto Mendez, Aditya Dandekar, Xuebao Zhang, Chunbin Zhang, Andrew C Liu, Lei Yin, Jiandie D Lin, Paul D Walker, Gregory Kapatos, Kezhong Zhang
Circadian clock orchestrates diverse physiological processes that are critical for health and disease. Cyclic AMP responsive element-binding protein, hepatocyte-specific (CREBH) is a liver-enriched, endoplasmic reticulum (ER)-tethered transcription factor known to regulate hepatic acute-phase response and energy homeostasis under stress conditions. Here, we demonstrate that CREBH is regulated by the circadian clock and functions as a circadian regulator of hepatic lipid metabolism. Proteolytic activation of CREBH in the liver exhibits typical circadian rhythmicity that is controlled by the core clock oscillator BMAL1 and AKT/GSK3β signaling pathway...
August 9, 2016: Diabetes
https://www.readbyqxmd.com/read/27492621/sec16-alternative-splicing-dynamically-controls-copii-transport-efficiency
#19
Ilka Wilhelmi, Regina Kanski, Alexander Neumann, Olga Herdt, Florian Hoff, Ralf Jacob, Marco Preußner, Florian Heyd
The transport of secretory proteins from the endoplasmic reticulum (ER) to the Golgi depends on COPII-coated vesicles. While the basic principles of the COPII machinery have been identified, it remains largely unknown how COPII transport is regulated to accommodate tissue- or activation-specific differences in cargo load and identity. Here we show that activation-induced alternative splicing of Sec16 controls adaptation of COPII transport to increased secretory cargo upon T-cell activation. Using splice-site blocking morpholinos and CRISPR/Cas9-mediated genome engineering, we show that the number of ER exit sites, COPII dynamics and transport efficiency depend on Sec16 alternative splicing...
2016: Nature Communications
https://www.readbyqxmd.com/read/27476655/arcn1-mutations-cause-a-recognizable-craniofacial-syndrome-due-to-copi-mediated-transport-defects
#20
Kosuke Izumi, Maggie Brett, Eriko Nishi, Séverine Drunat, Ee-Shien Tan, Katsunori Fujiki, Sophie Lebon, Breana Cham, Koji Masuda, Michiko Arakawa, Adeline Jacquinet, Yusuke Yamazumi, Shu-Ting Chen, Alain Verloes, Yuki Okada, Yuki Katou, Tomohiko Nakamura, Tetsu Akiyama, Pierre Gressens, Roger Foo, Sandrine Passemard, Ene-Choo Tan, Vincent El Ghouzzi, Katsuhiko Shirahige
Cellular homeostasis is maintained by the highly organized cooperation of intracellular trafficking systems, including COPI, COPII, and clathrin complexes. COPI is a coatomer protein complex responsible for intracellular protein transport between the endoplasmic reticulum and the Golgi apparatus. The importance of such intracellular transport mechanisms is underscored by the various disorders, including skeletal disorders such as cranio-lenticulo-sutural dysplasia and osteogenesis imperfect, caused by mutations in the COPII coatomer complex...
August 4, 2016: American Journal of Human Genetics
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