Read by QxMD icon Read


Yohei Ohashi, Nicolas Soler, Miguel García Ortegón, Lufei Zhang, Marie L Kirsten, Olga Perisic, Glenn R Masson, John E Burke, Arjen J Jakobi, Apostolos A Apostolakis, Christopher M Johnson, Maki Ohashi, Nicholas T Ktistakis, Carsten Sachse, Roger L Williams
The phosphatidylinositol 3-kinase Vps34 is part of several protein complexes. The structural organization of heterotetrameric complexes is starting to emerge, but little is known about organization of additional accessory subunits that interact with these assemblies. Combining hydrogen-deuterium exchange mass spectrometry (HDX-MS), X-ray crystallography and electron microscopy (EM), we have characterized Atg38 and its human ortholog NRBF2, accessory components of complex I consisting of Vps15-Vps34-Vps30/Atg6-Atg14 (yeast) and PIK3R4/VPS15-PIK3C3/VPS34-BECN1/Beclin 1-ATG14 (human)...
September 14, 2016: Autophagy
Xiaojun Tan, Narendra Thapa, Yihan Liao, Suyong Choi, Richard A Anderson
Autophagy is a regulated self-digestion pathway with fundamental roles in cell homeostasis and diseases. Autophagy is regulated by coordinated actions of a series of autophagy-related (ATG) proteins. The Barkor/ATG14(L)-VPS34 (a class III phosphatidylinositol 3-kinase) complex and its product phosphatidylinositol 3-phosphate [PtdIns(3)P] play key roles in autophagy initiation. ATG14 contains a C-terminal Barkor/ATG14(L) autophagosome-targeting sequence (BATS) domain that senses the curvature of PtdIns(3)P-containing membrane...
September 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
Yutaka Inaguma, Ayumi Matsumoto, Mariko Noda, Hidenori Tabata, Akihiko Maeda, Masahide Goto, Daisuke Usui, Eriko F Jimbo, Kiyoshi Kikkawa, Mamitaro Ohtsuki, Mariko Y Momoi, Hitoshi Osaka, Takanori Yamagata, Koh-Ichi Nagata
Class III phosphoinositide 3-kinase (PIK3C3 or mammalian vacuolar protein sorting 34 homolog, Vps34) regulates vesicular trafficking, autophagy, and nutrient sensing. Recently, we reported that PIK3C3 is expressed in mouse cerebral cortex throughout the developmental process, especially at early embryonic stage. We thus examined the role of PIK3C3 in the development of the mouse cerebral cortex. Acute silencing of PIK3C3 with in utero electroporation method caused positional defects of excitatory neurons during corticogenesis...
October 2016: Journal of Neurochemistry
Alejandra C Schoijet, Tamara Sternlieb, Guillermo D Alonso
Autophagy is a degradative process by which eukaryotic cells digest their own components to provide aminoacids that may function as energy source under nutritional stress conditions. There is experimental evidence for autophagy in parasitic protists belonging to the family Trypanosomatidae. However, few proteins implicated in this process have been characterized so far in these parasites. Moreover, it has been shown that autophagy is involved in Trypanosoma cruzi differentiation and thus might have a role in pathogenicity...
September 7, 2016: Journal of Eukaryotic Microbiology
Krisztina Hegedűs, Szabolcs Takáts, Attila Boda, András Jipa, Péter Nagy, Kata Varga, Attila L Kovács, Gábor Juhász
The small GTPase Rab5 promotes recruitment of the Ccz1-Mon1 guanosine exchange complex to endosomes to activate Rab7, which facilitates endosome maturation and fusion with lysosomes. How these factors function during autophagy is incompletely understood. Here we show that autophagosomes accumulate due to impaired fusion with lysosomes upon loss of the Ccz1-Mon1-Rab7 module in starved Drosophila fat cells. In contrast, autophagosomes generated in Rab5-null mutant cells normally fuse with lysosomes during the starvation response...
October 15, 2016: Molecular Biology of the Cell
Mingqun Lin, Hongyan Liu, Qingming Xiong, Hua Niu, Zhihui Cheng, Akitsugu Yamamoto, Yasuko Rikihisa
Ehrlichia chaffeensis is an obligatory intracellular bacterium that causes a potentially fatal emerging zoonosis, human monocytic ehrlichiosis. E. chaffeensis has a limited capacity for biosynthesis and metabolism and thus depends mostly on host-synthesized nutrients for growth. Although the host cell cytoplasm is rich with these nutrients, as E. chaffeensis is confined within the early endosome-like membrane-bound compartment, only host nutrients that enter the compartment can be used by this bacterium. How this occurs is unknown...
August 19, 2016: Autophagy
Mee-Sup Yoon, Cheol Soo Choi
Mammalian target of rapamycin (mTOR) controls cell growth and metabolism in response to nutrients, energy, and growth factors. Recent findings have placed the lysosome at the core of mTOR complex 1 (mTORC1) regulation by amino acids. Two parallel pathways, Rag GTPase-Ragulator and Vps34-phospholipase D1 (PLD1), regulate mTOR activation on the lysosome. This review describes the recent advances in understanding amino acid-induced mTOR signaling with a particular focus on the role of mTOR in insulin resistance...
2016: Experimental & Molecular Medicine
Qiulun Lu, Yufeng Yao, Zhenkun Hu, Changqing Hu, Qixue Song, Jian Ye, Chengqi Xu, Annabel Z Wang, Qiuyun Chen, Qing Kenneth Wang
AGGF1 is an angiogenic factor with therapeutic potential to treat coronary artery disease (CAD) and myocardial infarction (MI). However, the underlying mechanism for AGGF1-mediated therapeutic angiogenesis is unknown. Here, we show for the first time that AGGF1 activates autophagy, a housekeeping catabolic cellular process, in endothelial cells (ECs), HL1, H9C2, and vascular smooth muscle cells. Studies with Atg5 small interfering RNA (siRNA) and the autophagy inhibitors bafilomycin A1 (Baf) and chloroquine demonstrate that autophagy is required for AGGF1-mediated EC proliferation, migration, capillary tube formation, and aortic ring-based angiogenesis...
August 2016: PLoS Biology
Loredana Saveanu, Sophie Lotersztajn
No abstract text is available yet for this article.
September 1, 2016: American Journal of Physiology. Cell Physiology
Mee-Sup Yoon, Kook Son, Edwin Arauz, Jung Min Han, Sunghoon Kim, Jie Chen
Amino acid availability activates signaling by the mammalian target of rapamycin (mTOR) complex 1, mTORC1, a master regulator of cell growth. The class III PI-3-kinase Vps34 mediates amino acid signaling to mTORC1 by regulating lysosomal translocation and activation of the phospholipase PLD1. Here, we identify leucyl-tRNA synthetase (LRS) as a leucine sensor for the activation of Vps34-PLD1 upstream of mTORC1. LRS is necessary for amino acid-induced Vps34 activation, cellular PI(3)P level increase, PLD1 activation, and PLD1 lysosomal translocation...
August 9, 2016: Cell Reports
Jonathan M Backer
The Class III phosphoinositide 3-kinase Vps34 (vacuolar protein sorting 34) plays important roles in endocytic trafficking, macroautophagy, phagocytosis, cytokinesis and nutrient sensing. Recent studies have provided exciting new insights into the structure and regulation of this lipid kinase, and new cellular functions for Vps34 have emerged. This review critically examines the wealth of new data on this important enzyme, and attempts to integrate these findings with current models of Vps34 signalling.
August 1, 2016: Biochemical Journal
Zongwei Li, Ming Zhuang, Lichao Zhang, Xingnan Zheng, Peng Yang, Zhuoyu Li
High glucose-regulated protein 78 (GRP78) expression contributes to the acquisition of a wide range of phenotypic cancer hallmarks, and the pleiotropic oncogenic functions of GRP78 may result from its diverse subcellular distribution. Interestingly, GRP78 has been reported to be secreted from solid tumour cells, participating in cell-cell communication in the tumour microenvironment. However, the mechanism underlying this secretion remains elusive. Here, we report that GRP78 is secreted from colon cancer cells via exosomes...
2016: Scientific Reports
Juan Wang, Jun-Ying Zhou, Dhonghyo Kho, John J Reiners, Gen Sheng Wu
Accumulating evidence suggests that mitogen-activated protein kinases (MAPKs) regulate macroautophagy/autophagy. However, the involvement of dual-specificity protein phosphatases (DUSPs), endogenous inhibitors for MAPKs, in autophagy remains to be determined. Here we report that DUSP1/MKP-1, the founding member of the DUSP family, plays a critical role in regulating autophagy. Specifically, we demonstrate that DUSP1 knockdown by shRNA in human ovarian cancer CAOV3 cells and knockout in murine embryonic fibroblasts, increases both basal and rapamycin-increased autophagic flux...
October 2, 2016: Autophagy
Xiaochuan Liu, Aoli Wang, Xiaofei Liang, Juanjuan Liu, Fengming Zou, Cheng Chen, Zheng Zhao, Yuanxin Deng, Hong Wu, Ziping Qi, Beilei Wang, Li Wang, Feiyang Liu, Yunhe Xu, Wenchao Wang, Stacey M Fernandes, Richard M Stone, Ilene A Galinsky, Jennifer R Brown, Teckpeng Loh, James D Griffin, Shanchun Zhang, Ellen L Weisberg, Xin Zhang, Jing Liu, Qingsong Liu
PI3Kδ has been found to be over-expressed in B-Cell-related malignancies. Despite the clinical success of the first selective PI3Kδ inhibitor, CAL-101, inhibition of PI3Kδ itself did not show too much cytotoxic efficacy against cancer cells. One possible reason is that PI3Kδ inhibition induced autophagy that protects the cells from death. Since class III PI3K isoform PIK3C3/Vps34 participates in autophagy initiation and progression, we predicted that a PI3Kδ and Vps34 dual inhibitor might improve the anti-proliferative activity observed for PI3Kδ-targeted inhibitors...
July 18, 2016: Oncotarget
Ermes Candiello, Manuel Kratzke, Dirk Wenzel, Dan Cassel, Peter Schu
The σ1 subunit of the AP-1 clathrin-coated-vesicle adaptor-protein complex is expressed as three isoforms. Tissues express σ1A and one of the σ1B and σ1C isoforms. Brain is the tissue with the highest σ1A and σ1B expression. σ1B-deficiency leads to severe mental retardation, accumulation of early endosomes in synapses and fewer synaptic vesicles, whose recycling is slowed down. AP-1/σ1A and AP-1/σ1B regulate maturation of these early endosomes into multivesicular body late endosomes, thereby controlling synaptic vesicle protein transport into a degradative pathway...
2016: Scientific Reports
Nishant Mohan, Yi Shen, Milos Dokmanovic, Yukinori Endo, Dianne S Hirsch, Wen Jin Wu
VPS34 is reported to activate S6K1 and is implicated in regulating cell growth, the mechanisms of which remain elusive. Here, we describe novel mechanisms by which VPS34 upregulates mTOR/S6K1 activity via downregulating TSC2 protein and activating RheB activity. Specifically, upregulation of VPS34 lipid kinase increases local production of ptdins(3)p in the plasma membrane, which recruits PIKFYVE, a FYVE domain containing protein, to ptdins(3)p enriched regions of the plasma membrane, where VPS34 forms a protein complex with PIKFYVE and TSC1...
July 7, 2016: Oncotarget
Yong Jiang, Alec N Woosley, Nageswaran Sivalingam, Sneha Natarajan, Philip H Howe
Transforming growth factor-β (TGF-β) induces the expression of Disabled-2 (Dab2), an endocytic adaptor and tumour suppressor, concomitant with the induction of an epithelial-mesenchymal transition (EMT) in mammary epithelial cells. Here we show that following TGF-β-mediated EMT, sustained TGF-β treatment leads to proteolytic degradation of Dab2 by cathepsin B (CTSB), loss of the mesenchymal phenotype and induction of autophagy. CTSB inhibition or expression of a CTSB-resistant Dab2 mutant maintains Dab2 expression and shifts long-term TGF-β-treated cells from autophagy to apoptosis...
August 2016: Nature Cell Biology
Lindsey N Young, Kelvin Cho, Rosalie Lawrence, Roberto Zoncu, James H Hurley
The class III phosphatidylinositol 3-kinase complex I (PI3KC3-C1) is central to autophagy initiation. We previously reported the V-shaped architecture of the four-subunit version of PI3KC3-C1 consisting of VPS (vacuolar protein sorting) 34, VPS15, BECN1 (Beclin 1), and ATG (autophagy-related) 14. Here we show that a putative fifth subunit, nuclear receptor binding factor 2 (NRBF2), is a tightly bound component of the complex that profoundly affects its activity and architecture. NRBF2 enhances the lipid kinase activity of the catalytic subunit, VPS34, by roughly 10-fold...
July 19, 2016: Proceedings of the National Academy of Sciences of the United States of America
Jong-Hyuk Baek, Juneyoung Jung, Jeongbin Seo, Jeong Hee Kim, Joungmok Kim
As a scaffolding subunit of PIK3C3/VPS34 complex, Beclin 1 recruits a variety of proteins to class III phosphatidylinositol-3-kinase (VPS34), resulting in the formation of a distinct PIK3C3/VPS34 complex with a specific function. Therefore, the investigation of a number of Beclin 1 domains required for the protein-protein interactions will provide important clues to understand PIK3C3/VPS34 complex, of which Beclin1-VPS34 interaction is core unit. In the present study, we have designed the bacterial overexpression system for the Beclin 1 domain corresponding to VPS34 binding (Vps34-BD) and set up the denaturing purification protocol due to the massive aggregation of Vps34-BD in E...
June 30, 2016: Journal of Microbiology and Biotechnology
Anu Chaudhary, Mara Leite, Bridget R Kulasekara, Melissa A Altura, Cassandra Ogahara, Eli Weiss, Wenqing Fu, Marie-Pierre Blanc, Michael O'Keeffe, Cox Terhorst, Joshua M Akey, Samuel I Miller
Mutations in genes encoding autophagy proteins have been associated with human autoimmune diseases, suggesting that diversity in autophagy responses could be associated with disease susceptibility or severity. A cellular genome-wide association study (GWAS) screen was performed to explore normal human diversity in responses to rapamycin, a microbial product that induces autophagy. Cells from several human populations demonstrated variability in expression of a cell surface receptor, CD244 (SlamF4, 2B4), that correlated with changes in rapamycin-induced autophagy...
July 25, 2016: Current Biology: CB
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"