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https://www.readbyqxmd.com/read/29150658/differential-regulation-of-synaptic-ap-2-clathrin-vesicle-uncoating-in-synaptic-plasticity
#1
Ermes Candiello, Ratnakar Mishra, Bernhard Schmidt, Olaf Jahn, Peter Schu
AP-1/σ1B-deficiency causes X-linked intellectual disability. AP-1/σ1B -/- mice have impaired synaptic vesicle recycling, fewer synaptic vesicles and enhanced endosome maturation mediated by AP-1/σ1A. Despite defects in synaptic vesicle recycling synapses contain two times more endocytic AP-2 clathrin-coated vesicles. We demonstrate increased formation of two classes of AP-2/clathrin coated vesicles. One which uncoats readily and a second with a stabilised clathrin coat. Coat stabilisation is mediated by three molecular mechanisms: reduced recruitment of Hsc70 and synaptojanin1 and enhanced μ2/AP-2 phosphorylation and activation...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29145196/aqp2-abundance-is-regulated-by-the-e3-ligase-chip-via-hsp70
#2
Mariangela Centrone, Marianna Ranieri, Annarita Di Mise, Sante Princiero Berlingerio, Annamaria Russo, Peter M T Deen, Olivier Staub, Giovanna Valenti, Grazia Tamma
BACKGROUND/AIMS: AQP2 expression is mainly controlled by vasopressin-dependent changes in protein abundance which is in turn regulated by AQP2 ubiquitylation and degradation, however the proteins involved in these processes are largely unknown. Here, we investigated the potential role of the CHIP E3 ligase in AQP2 regulation. METHODS: MCD4 cells and kidney slices were used to study the involvement of the E3 ligase CHIP on AQP2 protein abundance by cell homogenization and immunoprecipitation followed by immunoblotting...
November 17, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29111393/cyclin-dependent-kinase-5-mediated-phosphorylation-of-chip-promotes-the-taif-dependent-death-pathway-in-rotenone-treated-cortical-neurons
#3
Chiho Kim, Juhyung Lee, Yeon Uk Ko, Young J Oh
Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase. Its dysregulation has been implicated in various neurodegenerative diseases. We previously reported that phosphorylation of the C-terminus of the Hsc70-interacting protein (CHIP) by Cdk5 promotes truncated apoptosis-inducing factor (tAIF)-mediated neuronal death induced by oxidative stress. Here, we determined whether this Cdk5-dependent cell death signaling pathway is present in experimental models of Parkinson's disease. First, we showed that rotenone activates Cdk5 in primary cultures of cortical neurons and causes tAIF-dependent neuronal cell death...
October 27, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29063205/steered-molecular-dynamics-simulation-of-the-binding-of-the-bovine-auxilin-j-domain-to-the-hsc70-nucleotide-binding-domain
#4
You-Lin Xue, Lei Zhou, Yuna Sun, Hui Li, Gary W Jones, Youtao Song
The Hsp70 and Hsp40 chaperone machine plays critical roles in protein folding, membrane translocation, and protein degradation by binding and releasing protein substrates in a process that utilizes ATP. The activities of the Hsp70 family of chaperones are recruited and stimulated by the J domains of Hsp40 chaperones. However, structural information on the Hsp40-Hsp70 complex is lacking, and the molecular details of this interaction are yet to be elucidated. Here we used steered molecular dynamics (SMD) simulations to investigate the molecular interactions that occur during the dissociation of the auxilin J domain from the Hsc70 nucleotide-binding domain (NBD)...
October 23, 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/29034430/ultraviolet-filters-and-heat-shock-proteins-effects-in-chironomus-riparius-by-benzophenone-3-and-4-methylbenzylidene-camphor
#5
Raquel Martín-Folgar, Mónica Aquilino, Irene Ozáez, José-Luis Martínez-Guitarte
Benzophenone-3 (BP3) and 4-methylbenzylidene camphor (4MBC) are common ultraviolet filters (UV filters), compounds considered as emergent contaminants, used in different products like plastics and personal care products. The levels of these compounds are rising in the wild, but the effects they have on invertebrates are poorly understood. Chironomus riparius is a benthic insect widely used in toxicology, and several studies have been previously performed in our laboratory to determine the effects these compounds have on this organism at the molecular level...
October 16, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29027377/contribution-of-extracellular-matrix-and-signal-mechanotransduction-to-epithelial-cell-damage-in-inflammatory-bowel-disease-patients-a-proteomic-study
#6
Manuela Moriggi, Luca Pastorelli, Enrica Torretta, Gian Eugenio Tontini, Daniele Capitanio, Stefano Ferrero Bogetto, Maurizio Vecchi, Cecilia Gelfi
This study utilized 2D-DIGE, isotope-coded protein labelling (ICPL) and biochemical assays to characterize protein alteration in Ulcerative Colitis (UC) and Crohn's Disease (CD) in human epithelial cell and mucosal biopsies in Inflammatory Bowel Disease (IBD)-affected patients. The aim of this study is to identify the key molecular signatures involved in epithelial cell structure of IBDs. In non-inflamed UC (QUC) keratins, vimentin and FAK increased, whereas vinculin and de-tyrosinated α-tubulin decreased; inflammation (IUC) exacerbated molecular changes, being COL6A1, tenascin-C and vimentin increased...
October 13, 2017: Proteomics
https://www.readbyqxmd.com/read/29024389/in-vivo-properties-of-the-disaggregase-function-of-j-proteins-and-hsc70-in-caenorhabditis-elegans-stress-and-aging
#7
Janine Kirstein, Kristin Arnsburg, Annika Scior, Anna Szlachcic, D Lys Guilbride, Richard I Morimoto, Bernd Bukau, Nadinath B Nillegoda
Protein aggregation is enhanced upon exposure to various stress conditions and aging, which suggests that the quality control machinery regulating protein homeostasis could exhibit varied capacities in different stages of organismal lifespan. Recently, an efficient metazoan disaggregase activity was identified in vitro, which requires the Hsp70 chaperone and Hsp110 nucleotide exchange factor, together with single or cooperating J-protein co-chaperones of classes A and B. Here, we describe how the orthologous Hsp70s and J-protein of Caenorhabditis elegans work together to resolve protein aggregates both in vivo and in vitro to benefit organismal health...
December 2017: Aging Cell
https://www.readbyqxmd.com/read/29021755/dj-1-inhibits-%C3%AE-synuclein-aggregation-by-regulating-chaperone-mediated-autophagy
#8
Chuan-Ying Xu, Wen-Yan Kang, Yi-Meng Chen, Tian-Fang Jiang, Jia Zhang, Li-Na Zhang, Jian-Qing Ding, Jun Liu, Sheng-Di Chen
α-Synuclein misfolding and aggregation play an important role in the pathogenesis of Parkinson's disease (PD). Loss of function and mutation of the PARK7/DJ-1 gene cause early-onset familial PD. DJ-1 can inhibit α-synuclein aggregation, and may function at an early step in the aggregation process. Soluble wild-type (WT) α-synuclein is mainly degraded by chaperone-mediated autophagy (CMA), and impairment of CMA is closely related to the pathogenesis of PD. Here, we investigated whether DJ-1 could reduce α-synuclein accumulation and aggregation by CMA...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29016855/enhanced-tau-pathology-via-ranbp9-and-hsp90-hsc70-chaperone-complexes
#9
Jung A Woo, Tian Liu, Xingyu Zhao, Courtney Trotter, Ksenia Yrigoin, Sara Cazzaro, Emilio De Narvaez, Hirah Khan, Richard Witas, Anusha Bukhari, Kamal Makati, Xinming Wang, Chad Dickey, David E Kang
Accumulation of amyloid β (Aβ) and tau represent the two major pathological hallmarks of Alzheimer's disease (AD). Despite the critical importance of Aβ accumulation as an early event in AD pathogenesis, multiple lines of evidence indicate that tau is required to mediate Aβ-induced neurotoxic signals in neurons. We have previously shown that the scaffolding protein Ran-binding protein 9 (RanBP9), which is highly elevated in brains of AD and AD mouse models, both enhances Aβ production and mediates Aβ-induced neurotoxicity...
October 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28991259/impaired-p65-degradation-by-decreased-chaperone-mediated-autophagy-activity-facilitates-epithelial-to-mesenchymal-transition
#10
J Tang, M-N Zhan, Q-Q Yin, C-X Zhou, C-L Wang, L-L Wo, M He, G-Q Chen, Q Zhao
Aberrant activation of nuclear factor-κB (NF-κB) has been observed in a wide range of human cancers and is thought to promote tumorigenesis and metastasis. As a central component of NF-κB pathway, p65 protein level is tightly regulated and could be subjected to proteasome degradation. Here we demonstrated that p65 can bind to HSC70 with four consensus recognition motif in its RHD domain and be constitutively transported to the lysosome membrane to bind with lysosome-associated membrane protein type 2A and degraded within the lysosome in two epithelial cell lines, proposing that p65 can be degraded by chaperone-mediated autophagy (CMA)...
October 9, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28980748/hikeshi-modulates-the-proteotoxic-stress-response-in-human-cells-implication-for-the-importance-of-the-nuclear-function-of-hsp70s
#11
Khondoker Md Zulfiker Rahman, Hiroshi Mamada, Masatoshi Takagi, Shingo Kose, Naoko Imamoto
Hikeshi mediates the heat stress-induced nuclear import of heat-shock protein 70 (HSP70s: HSP70/HSC70). Dysfunction of Hikeshi causes some serious effects in humans; however, the cellular function of Hikeshi is largely unknown. Here, we investigated the effects of Hikeshi depletion on the survival of human cells after proteotoxic stress and found opposite effects in HeLa and hTERT-RPE1 (RPE) cells; depletion of Hikeshi reduced the survival of HeLa cells, but increased the survival of RPE cells in response to proteotoxic stress...
October 5, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28978466/post-transcriptional-inhibition-of-hsc70-4-hspa8-expression-leads-to-synaptic-vesicle-cycling-defects-in-multiple-models-of-als
#12
Alyssa N Coyne, Ileana Lorenzini, Ching-Chieh Chou, Meaghan Torvund, Robert S Rogers, Alexander Starr, Benjamin L Zaepfel, Jennifer Levy, Jeffrey Johannesmeyer, Jacob C Schwartz, Hiroshi Nishimune, Konrad Zinsmaier, Wilfried Rossoll, Rita Sattler, Daniela C Zarnescu
Amyotrophic lateral sclerosis (ALS) is a synaptopathy accompanied by the presence of cytoplasmic aggregates containing TDP-43, an RNA-binding protein linked to ∼97% of ALS cases. Using a Drosophila model of ALS, we show that TDP-43 overexpression (OE) in motor neurons results in decreased expression of the Hsc70-4 chaperone at the neuromuscular junction (NMJ). Mechanistically, mutant TDP-43 sequesters hsc70-4 mRNA and impairs its translation. Expression of the Hsc70-4 ortholog, HSPA8, is also reduced in primary motor neurons and NMJs of mice expressing mutant TDP-43...
October 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28971854/in-vitro-reconstitution-of-chaperone-mediated-human-risc-assembly
#13
Ken Naruse, Eriko Matsuura-Suzuki, Mariko Watanabe, Shintaro Iwasaki, Yukihide Tomari
To silence target mRNAs, small RNAs and Argonaute (Ago) proteins need to be assembled into RNA-induced silencing complexes (RISCs). Although the assembly of Drosophila melanogaster RISC was recently reconstituted by Ago2, the Dicer-2/R2D2 heterodimer, and 5 chaperone proteins, the absence of a reconstitution system for mammalian RISC assembly has posed analytical challenges. Here we describe reconstitution of human RISC assembly using Ago2 and 5 recombinant chaperone proteins: Hsp90β, Hsc70, Hop, Dnaja2, and p23...
October 2, 2017: RNA
https://www.readbyqxmd.com/read/28966044/hdac6-suppresses-age-dependent-ectopic-fat-accumulation-by-maintaining-the-proteostasis-of-plin2-in-drosophila
#14
Yan Yan, Hao Wang, Minling Hu, Lifen Jiang, Yang Wang, Pingsheng Liu, Xuehong Liang, Jiyong Liu, Changqing Li, Anya Lindström-Battle, Sin Man Lam, Guanghou Shui, Wu-Min Deng, Renjie Jiao
Age-dependent ectopic fat accumulation (EFA) in animals contributes to the progression of tissue aging and diseases such as obesity, diabetes, and cancer. However, the primary causes of age-dependent EFA remain largely elusive. Here, we characterize the occurrence of age-dependent EFA in Drosophila and identify HDAC6, a cytosolic histone deacetylase, as a suppressor of EFA. Loss of HDAC6 leads to significant age-dependent EFA, lipid composition imbalance, and reduced animal longevity on a high-fat diet. The EFA and longevity phenotypes are ameliorated by a reduction of the lipid-droplet-resident protein PLIN2...
October 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28944418/endogenous-epitope-tagging-of-heat-shock-protein-70-isoform-hsc70-using-crispr-cas9
#15
Nitika, Andrew W Truman
Heat shock protein 70 (Hsp70) is an evolutionarily well-conserved molecular chaperone involved in several cellular processes such as folding of proteins, modulating protein-protein interactions, and transport of proteins across the membrane. Binding partners of Hsp70 (known as "clients") are identified on an individual basis as researchers discover their particular protein of interest binds to Hsp70. A full complement of Hsp70 interactors under multiple stress conditions remains to be determined. A promising approach to characterizing the Hsp70 "interactome" is the use of protein epitope tagging and then affinity purification followed by mass spectrometry (AP-MS/MS)...
September 24, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28939948/heat-shock-cognate-70-gene-in-haliotis-diversicolor-responses-to-pathogen-infection-and-environmental-stresses-and-its-transcriptional-regulation-analysis
#16
Yuting Li, Tao Zhang, Xin Zhang, Guodong Wang, Yilei Wang, Ziping Zhang
Heat shock cognate 70 (HSC70) is a class of highly conserved proteins which functions as a molecular chaperon, participates in tolerance processes, and is involved in protein folding, degradation, targeting, translocation, and protein complex remodeling. In this study, the mRNA expression level of the Haliotis diversicolor HSC70 (HdHSC70) gene was detected by quantitative real-time PCR in different tissues and under different stresses. The results showed that the HdHSC70 gene was ubiquitously expressed in seven selected tissues...
September 23, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28881949/heat-tolerance-induction-of-the-indian-meal-moth-lepidoptera-pyralidae-is-accompanied-by-upregulation-of-heat-shock-proteins-and-polyols
#17
Minhyun Kim, Seunghee Lee, Yong Shik Chun, Jahyun Na, Hyeok Kwon, Wook Kim, Yonggyun Kim
The Indian meal moth, Plodia interpunctella, causes massive damage to stored grains and processed foods. Heat treatment has been widely used to control insect pests infesting stored grains. However, heat treatment may result in unsatisfactory control owing to heat tolerance of target insects. This study quantified the heat tolerance and analyzed its induction in P. interpunctella. Susceptibility of P. interpunctella to different high temperatures was assessed in all developmental stages. Heat treatment at 44 °C for 1 h caused significant mortalities to all developmental stages, with late-instar larvae exhibiting the highest tolerance...
August 1, 2017: Environmental Entomology
https://www.readbyqxmd.com/read/28855547/tylophorine-analogs-allosterically-regulates-heat-shock-cognate-protein-70-and-inhibits-hepatitis-c-virus-replication
#18
Ying Wang, Sangwon Lee, Ya Ha, Wing Lam, Shao-Ru Chen, Ginger E Dutschman, Elizabeth A Gullen, Susan P Grill, Yao Cheng, Alois Fürstner, Samson Francis, David C Baker, Xiaoming Yang, Kuo-Hsiung Lee, Yung-Chi Cheng
Tylophorine analogs have been shown to exhibit diverse activities against cancer, inflammation, arthritis, and lupus in vivo. In this study, we demonstrated that two tylophorine analogs, DCB-3503 and rac-cryptopleurine, exhibit potent inhibitory activity against hepatitis C virus (HCV) replication in genotype 1b Con 1 isolate. The inhibition of HCV replication is at least partially mediated through cellular heat shock cognate protein 70 (Hsc70). Hsc70 associates with the HCV replication complex by primarily binding to the poly U/UC motifs in HCV RNA...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28855508/chaperones-rescue-the-energetic-landscape-of-mutant-cftr-at-single-molecule-and-in-cell
#19
Miklos Bagdany, Guido Veit, Ryosuke Fukuda, Radu G Avramescu, Tsukasa Okiyoneda, Imad Baaklini, Jay Singh, Guy Sovak, Haijin Xu, Pirjo M Apaja, Sara Sattin, Lenore K Beitel, Ariel Roldan, Giorgio Colombo, William Balch, Jason C Young, Gergely L Lukacs
Molecular chaperones are pivotal in folding and degradation of the cellular proteome but their impact on the conformational dynamics of near-native membrane proteins with disease relevance remains unknown. Here we report the effect of chaperone activity on the functional conformation of the temperature-sensitive mutant cystic fibrosis channel (∆F508-CFTR) at the plasma membrane and after reconstitution into phospholipid bilayer. Thermally induced unfolding at 37 °C and concomitant functional inactivation of ∆F508-CFTR are partially suppressed by constitutive activity of Hsc70 and Hsp90 chaperone/co-chaperone at the plasma membrane and post-endoplasmic reticulum compartments in vivo, and at single-molecule level in vitro, indicated by kinetic and thermodynamic remodeling of the mutant gating energetics toward its wild-type counterpart...
August 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28851515/alterations-in-the-e3-ligases-parkin-and-chip-result-in-unique-metabolic-signaling-defects-and-mitochondrial-quality-control-issues
#20
REVIEW
Britney N Lizama, Amy M Palubinsky, BethAnn McLaughlin
E3 ligases are essential scaffold proteins, facilitating the transfer of ubiquitin from E2 enzymes to lysine residues of client proteins via isopeptide bonds. The specificity of substrate binding and the expression and localization of E3 ligases can, however, endow these proteins with unique features with variable effects on mitochondrial, metabolic and CNS function. By comparing and contrasting two E3 ligases, Parkin and C-terminus of HSC70-Interacting protein (CHIP) we seek to highlight the biophysical properties that may promote mitochondrial dysfunction, acute stress signaling and critical developmental periods to cease in response to mutations in these genes...
August 26, 2017: Neurochemistry International
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