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https://www.readbyqxmd.com/read/27648578/autophagy-linked-fyve-alfy-wdfy3-is-required-for-establishing-neuronal-connectivity-in-the-mammalian-brain
#1
Joanna M Dragich, Takaaki Kuwajima, Megumi Hirose-Ikeda, Michael S Yoon, Evelien Eenjes, Joan R Bosco, Leora M Fox, Alf H Lystad, Tinmarla F Oo, Olga Yarygina, Tomohiro Mita, Satoshi Waguri, Yoshinobu Ichimura, Masaaki Komatsu, Anne Simonsen, Robert E Burke, Carol A Mason, Ai Yamamoto
The regulation of protein degradation is essential for maintaining the appropriate environment to coordinate complex cell signaling events and to promote cellular remodeling. The Autophagy linked FYVE protein (Alfy), previously identified as a molecular scaffold between the ubiquitinated cargo and the autophagic machinery, is highly expressed in the developing central nervous system, indicating that this pathway may have yet unexplored roles in neurodevelopment. To examine this possibility, we used mouse genetics to eliminate Alfy expression...
September 20, 2016: ELife
https://www.readbyqxmd.com/read/27605931/an-arabidopsis-zinc-finger-protein-increases-abiotic-stress-tolerance-by-regulating-sodium-and-potassium-homeostasis-reactive-oxygen-species-scavenging-and-osmotic-potential
#2
Dandan Zang, Hongyan Li, Hongyun Xu, Wenhui Zhang, Yiming Zhang, Xinxin Shi, Yucheng Wang
Plant zinc finger proteins (ZFPs) comprise a large protein family and they are mainly involved in abiotic stress tolerance. Although Arabidopsis RING/FYVE/PHD ZFP At5g62460 (AtRZFP) is found to bind to zinc, whether it is involved in abiotic stress tolerance is still unknown. In the present study, we characterized the roles of AtRZFP in response to abiotic stresses. The expression of AtRZFP was induced significantly by salt and osmotic stress. AtRZFP positively mediates tolerance to salt and osmotic stress...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27409169/vps34-regulates-tsc1-tsc2-heterodimer-to-mediate-rheb-and-mtorc1-s6k1-activation-and-cellular-transformation
#3
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
https://www.readbyqxmd.com/read/27391591/phosphoinositide-binding-proteins-in-autophagy
#4
REVIEW
Alf Håkon Lystad, Anne Simonsen
Phosphoinositides represent a very small fraction of membrane phospholipids, having fast turnover rates and unique subcellular distributions, which make them perfect for initiating local temporal effects. Seven different phosphoinositide species are generated through reversible phosphorylation of the inositol ring of phosphatidylinositol (PtdIns). The negative charge generated by the phosphates provides specificity for interaction with various protein domains that commonly contain a cluster of basic residues...
August 2016: FEBS Letters
https://www.readbyqxmd.com/read/27330028/autophagy-linked-fyve-containing-protein-wdfy3-interacts-with-traf6-and-modulates-rankl-induced-osteoclastogenesis
#5
Dennis J Wu, Ran Gu, Ritu Sarin, Regina Zavodovskaya, Chia-Pei Chen, Blaine A Christiansen, Iannis E Adamopoulos
Recently, autophagy-related proteins were shown to regulate osteoclast mediated bone resorption, a critical process in autoimmune diseases such as rheumatoid arthritis. However, the role of autophagy-linked FYVE containing protein, WDFY3, in osteoclast biology remains elusive. WDFY3 is a master regulator in selective autophagy for clearing ubiquitinated protein aggregates and has been linked with rheumatoid arthritis. Herein, we used a series of WDFY3 transgenic mice (Wdfy3(lacZ) and Wdfy3(loxP)) to investigate the function of WDFY3 in osteoclast development and function...
September 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27246247/structural-basis-of-fyco1-and-map1lc3a-interaction-reveals-a-novel-binding-mode-for-atg8-family-proteins
#6
Xiaofang Cheng, Yingli Wang, Yukang Gong, Faxiang Li, Yujiao Guo, Shichen Hu, Jianping Liu, Lifeng Pan
FYCO1 (FYVE and coiled-coil domain containing 1) functions as an autophagy adaptor in directly linking autophagosomes with the microtubule-based kinesin motor, and plays an essential role in the microtubule plus end-directed transport of autophagic vesicles. The specific association of FYCO1 with autophagosomes is mediated by its interaction with Atg8-family proteins decorated on the outer surface of autophagosome. However, the mechanistic basis governing the interaction between FYCO1 and Atg8-family proteins is largely unknown...
August 2, 2016: Autophagy
https://www.readbyqxmd.com/read/27026195/nrp2-transcriptionally-regulates-its-downstream-effector-wdfy1
#7
Samikshan Dutta, Sohini Roy, Navatha S Polavaram, Gustavo B Baretton, Michael H Muders, Surinder Batra, Kaustubh Datta
Neuropilins (NRPs) are cell surface glycoproteins that often act as co-receptors for plexins and VEGF family receptors. Neuropilin-2 (NRP2), a family member of NRPs, was shown to regulate autophagy and endocytic trafficking in cancer cells, a function distinctly different from its role as a co-receptor. WD Repeat and FYVE domain containing 1 (WDFY1)-protein acts downstream of NRP2 for this function. Our results indicated that NRP2 maintains an optimum concentration of WDFY1 by negatively regulating its expression...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27005890/endometrial-vezatin-and-its-association-with-endometriosis-risk
#8
Sarah J Holdsworth-Carson, Jenny N Fung, Hien T T Luong, Yadav Sapkota, Lisa M Bowdler, Leanne Wallace, Wan Tinn Teh, Joseph E Powell, Jane E Girling, Martin Healey, Grant W Montgomery, Peter A W Rogers
STUDY QUESTION: Do endometriosis risk-associated single nucleotide polymorphisms (SNPs) found at the 12q22 locus have effects on vezatin ( ITALIC! VEZT) expression? SUMMARY ANSWER: The original genome-wide association study (GWAS) SNP (rs10859871), and other newly identified association signals, demonstrate strong evidence for ITALIC! cis-expression quantitative trait loci (eQTL) effects on ITALIC! VEZT expression. WHAT IS KNOWN ALREADY: GWAS have identified several disease-risk loci (SNPs) associated with endometriosis...
May 2016: Human Reproduction
https://www.readbyqxmd.com/read/26971885/endosomal-sorting-complexes-required-for-transport-0-is-essential-for-fungal-development-and-pathogenicity-in-fusarium-graminearum
#9
Qiurong Xie, Ahai Chen, Wenhui Zheng, Huaijian Xu, Wenjie Shang, Huawei Zheng, Dongmei Zhang, Jie Zhou, Guodong Lu, Guangpu Li, Zonghua Wang
Fusarium graminearum is an important plant pathogen that causes head blight of major cereal crops. The vacuolar protein sorting (Vps) protein Vps27 is a component of ESCRT-0 involved in the multivesicular body (MVB) sorting pathway during endocytosis. In this study, we investigated the function of FgVps27 using a gene replacement strategy. The FgVPS27 deletion mutant (ΔFgvps27) exhibited a reduction in growth rate, aerial hyphae formation and hydrophobicity. It also showed increased sensitivity to cell wall-damaging agents and to osmotic stresses...
November 2016: Environmental Microbiology
https://www.readbyqxmd.com/read/26658939/hnrnph1-is-a-quantitative-trait-gene-for-methamphetamine-sensitivity
#10
Neema Yazdani, Clarissa C Parker, Ying Shen, Eric R Reed, Michael A Guido, Loren A Kole, Stacey L Kirkpatrick, Jackie E Lim, Greta Sokoloff, Riyan Cheng, W Evan Johnson, Abraham A Palmer, Camron D Bryant
Psychostimulant addiction is a heritable substance use disorder; however its genetic basis is almost entirely unknown. Quantitative trait locus (QTL) mapping in mice offers a complementary approach to human genome-wide association studies and can facilitate environment control, statistical power, novel gene discovery, and neurobiological mechanisms. We used interval-specific congenic mouse lines carrying various segments of chromosome 11 from the DBA/2J strain on an isogenic C57BL/6J background to positionally clone a 206 kb QTL (50,185,512-50,391,845 bp) that was causally associated with a reduction in the locomotor stimulant response to methamphetamine (2 mg/kg, i...
December 2015: PLoS Genetics
https://www.readbyqxmd.com/read/26560516/neuropilin-2-regulates-endosome-maturation-and-egfr-trafficking-to-support-cancer-cell-pathobiology
#11
Samikshan Dutta, Sohini Roy, Navatha S Polavaram, Marissa J Stanton, Heyu Zhang, Tanvi Bhola, Pia Hönscheid, Terrence M Donohue, Hamid Band, Surinder K Batra, Michael H Muders, Kaustubh Datta
Neuropilin-2 (NRP2) is a non-tyrosine kinase receptor frequently overexpressed in various malignancies, where it has been implicated in promoting many protumorigenic behaviors, such as imparting therapeutic resistance to metastatic cancer cells. Here, we report a novel function of NRP2 as a regulator of endocytosis, which is enhanced in cancer cells and is often associated with increased metastatic potential and drug resistance. We found that NRP2 depletion in human prostate and pancreatic cancer cells resulted in the accumulation of EEA1/Rab5-positive early endosomes concomitant with a decrease in Rab7-positive late endosomes, suggesting a delay in early-to-late endosome maturation...
January 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/26510498/a-lapf-phafin1-like-protein-regulates-torc1-and-lysosomal-membrane-permeabilization-in-response-to-endoplasmic-reticulum-membrane-stress
#12
Adam Kim, Kyle W Cunningham
Lysosomal membrane permeabilization (LMP) is a poorly understood regulator of programmed cell death that involves leakage of luminal lysosomal or vacuolar hydrolases into the cytoplasm. In Saccharomyces cerevisiae, LMP can be induced by antifungals and endoplasmic reticulum stressors when calcineurin also has been inactivated. A genome-wide screen revealed Pib2, a relative of LAPF/phafin1 that regulates LMP in mammals, as a pro-LMP protein in yeast. Pib2 associated with vacuolar and endosomal limiting membranes in unstressed cells in a manner that depended on its FYVE domain and on phosphatidylinositol 3-phosphate (PI(3)P) biosynthesis...
December 15, 2015: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/26468287/fyco1-contains-a-c-terminally-extended-lc3a-b-preferring-lc3-interacting-region-lir-motif-required-for-efficient-maturation-of-autophagosomes-during-basal-autophagy
#13
Hallvard L Olsvik, Trond Lamark, Kenji Takagi, Kenneth Bowitz Larsen, Gry Evjen, Aud Øvervatn, Tsunehiro Mizushima, Terje Johansen
FYCO1 (FYVE and coiled-coil protein 1) is a transport adaptor that binds to phosphatidylinositol 3-phosphate, to Rab7, and to LC3 (microtubule-associated protein 1 light chain 3) to mediate transport of late endosomes and autophagosomes along microtubules in the plus end direction. We have previously shown that FYCO1 binds to LC3B via a 19-amino acid sequence containing a putative core LC3-interacting region (LIR) motif. Here, we show that FYCO1 preferentially binds to LC3A and -B. By peptide array-based two-dimensional mutational scans of the binding to LC3B, we found FYCO1 to contain a C-terminally extended LIR domain...
December 4, 2015: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/26407065/transcriptome-wide-identification-of-reference-genes-for-expression-analysis-of-soybean-responses-to-drought-stress-along-the-day
#14
Juliana Marcolino-Gomes, Fabiana Aparecida Rodrigues, Renata Fuganti-Pagliarini, Thiago Jonas Nakayama, Rafaela Ribeiro Reis, Jose Renato Bouças Farias, Frank G Harmon, Hugo Bruno Correa Molinari, Mayla Daiane Correa Molinari, Alexandre Nepomuceno
The soybean transcriptome displays strong variation along the day in optimal growth conditions and also in response to adverse circumstances, like drought stress. However, no study conducted to date has presented suitable reference genes, with stable expression along the day, for relative gene expression quantification in combined studies on drought stress and diurnal oscillations. Recently, water deficit responses have been associated with circadian clock oscillations at the transcription level, revealing the existence of hitherto unknown processes and increasing the demand for studies on plant responses to drought stress and its oscillation during the day...
2015: PloS One
https://www.readbyqxmd.com/read/26358513/endofin-a-novel-bmp-smad-regulator-of-the-iron-regulatory-hormone-hepcidin
#15
Justin B Goh, Daniel F Wallace, Wanjin Hong, V Nathan Subramaniam
BMP-SMAD signalling plays a crucial role in numerous biological processes including embryonic development and iron homeostasis. Dysregulation of the iron-regulatory hormone hepcidin is associated with many clinical iron-related disorders. We hypothesised that molecules which mediate BMP-SMAD signalling play important roles in the regulation of iron homeostasis and variants in these proteins may be potential genetic modifiers of iron-related diseases. We examined the role of endofin, a SMAD anchor, and show that knockdown of endofin in liver cells inhibits basal and BMP-induced hepcidin expression along with other BMP-regulated genes, ID1 and SMAD7...
2015: Scientific Reports
https://www.readbyqxmd.com/read/26302821/a-microrna-signature-in-gestational-diabetes-mellitus-associated-with-risk-of-macrosomia
#16
Jiandong Li, Liping Song, Ling Zhou, Jiaoxiang Wu, Chunjie Sheng, Huiming Chen, Yanjun Liu, Shijuan Gao, Wenlin Huang
BACKGROUND/AIMS: MicroRNA (miRNA) is a small non-coding RNA molecule that functions in regulation of gene expression by targeting mRNA to affect its stability and/or translation. The aim of this study was to evaluate the miRNAs involvement in gestational diabetes mellitus (GDM), a well known risk factor for fetal overgrowth. METHODS: Differential microRNA expression in placental tissues of normal controls and women with GDM were identified by miRNA micorarray analysis and further confirmed by quantitative real-time PCR (qRT-PCR) on an independent set of normal and GDM placental tissues...
2015: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/26165498/fast-suppressor-screening-for-new-components-in-protein-trafficking-organelle-biogenesis-and-silencing-pathway-in-arabidopsis-thaliana-using-dex-inducible-free1-rnai-plants
#17
Qiong Zhao, Caiji Gao, PoShing Lee, Lin Liu, Shaofang Li, Tangjin Hu, Jinbo Shen, Shuying Pan, Hao Ye, Yunru Chen, Wenhan Cao, Yong Cui, Peng Zeng, Sheng Yu, Yangbin Gao, Liang Chen, Beixin Mo, Xin Liu, Shi Xiao, Yunde Zhao, Silin Zhong, Xuemei Chen, Liwen Jiang
Membrane trafficking is essential for plant growth and responses to external signals. The plant unique FYVE domain-containing protein FREE1 is a component of the ESCRT complex (endosomal sorting complex required for transport). FREE1 plays multiple roles in regulating protein trafficking and organelle biogenesis including the formation of intraluminal vesicles of multivesicular body (MVB), vacuolar protein transport and vacuole biogenesis, and autophagic degradation. FREE1 knockout plants show defective MVB formation, abnormal vacuolar transport, fragmented vacuoles, accumulated autophagosomes, and seedling lethality...
June 20, 2015: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/26086452/drosophila-gyf-grb10-interacting-gyf-protein-is-an-autophagy-regulator-that-controls-neuron-and-muscle-homeostasis
#18
Myungjin Kim, Ian Semple, Boyoung Kim, Alexandra Kiers, Samuel Nam, Hwan-Woo Park, Haeli Park, Seung-Hyun Ro, Jeong-Sig Kim, Gábor Juhász, Jun Hee Lee
Autophagy is an essential process for eliminating ubiquitinated protein aggregates and dysfunctional organelles. Defective autophagy is associated with various degenerative diseases such as Parkinson disease. Through a genetic screening in Drosophila, we identified CG11148, whose product is orthologous to GIGYF1 (GRB10-interacting GYF protein 1) and GIGYF2 in mammals, as a new autophagy regulator; we hereafter refer to this gene as Gyf. Silencing of Gyf completely suppressed the effect of Atg1-Atg13 activation in stimulating autophagic flux and inducing autophagic eye degeneration...
2015: Autophagy
https://www.readbyqxmd.com/read/25985087/a-fyve-zinc-finger-domain-protein-specifically-links-mrna-transport-to-endosome-trafficking
#19
Thomas Pohlmann, Sebastian Baumann, Carl Haag, Mario Albrecht, Michael Feldbrügge
An emerging theme in cellular logistics is the close connection between mRNA and membrane trafficking. A prominent example is the microtubule-dependent transport of mRNAs and associated ribosomes on endosomes. This coordinated process is crucial for correct septin filamentation and efficient growth of polarised cells, such as fungal hyphae. Despite detailed knowledge on the key RNA-binding protein and the molecular motors involved, it is unclear how mRNAs are connected to membranes during transport. Here, we identify a novel factor containing a FYVE zinc finger domain for interaction with endosomal lipids and a new PAM2-like domain required for interaction with the MLLE domain of the key RNA-binding protein...
2015: ELife
https://www.readbyqxmd.com/read/25876663/cellular-localization-and-tissue-distribution-of-endogenous-dfcp1-protein
#20
Tomohisa Nanao, Masato Koike, Junji Yamaguchi, Mitsuho Sasaki, Yasuo Uchiyama
Autophagy is essential for the maintenance of cellular metabolism. Once autophagy is induced in cells, the isolation membrane forms a so-called phagophore. The endoplasmic reticulum (ER) is one of several candidates for the membrane source for phagophores. Recently, LC3-positive isolation membranes were found to emerge from a DFCP1 (double FYVE domain-containing protein)-positive, ER-associated compartment called the omegasome. Although the GFP-tagged DFCP1 protein has been examined in cultured cells, little is known about the precise cellular and tissue distribution of this endogenous protein...
2015: Biomedical Research
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