Correction: Differential androgen deprivation therapies with anti-androgens Casodex/bicalutamide or MDV3100/enzalutamide versus anti-androgen receptor ASC-J9(R) lead to promotion versus suppression of prostate cancer metastasis [Additions and Corrections]
VOLUME 288 (2013) PAGES 19359–19369For Fig. 5E, in the last row stained for PSA, one of the images in the MDV group was mistakenly inserted as the ASC group with a vertical translation during article preparation. The correct images from the MDV group and ASC group are presented in the corrected figure. We sincerely apologize for the error, and we assure that the correction of the images will not alter the original results or conclusions.jbc;295/46/15796/F5F1F5Figure 5E. (Source: Journal of Biological Chemistry)
Source: Journal of Biological Chemistry - November 13, 2020 Category: Chemistry Authors: Tzu-Hua Lin, Soo Ok Lee, Yuanjie Niu, Defeng Xu, Liang Liang, Lei Li, Shauh-Der Yeh, Naohiro Fujimoto, Shuyuan Yeh, Chawnshang Chang Tags: Additions and Corrections Source Type: research

Correction: Genetic disruption of the small GTPase RAC1 prevents plexiform neurofibroma formation in mice with neurofibromatosis type 17 [Additions and Corrections]
VOLUME 295 (2020) PAGES 9948–9958There was an inadvertent typo on the title of this article. It should read: “Genetic disruption of the small GTPase RAC1 prevents plexiform neurofibroma formation in mice with neurofibromatosis type 1.” (Source: Journal of Biological Chemistry)
Source: Journal of Biological Chemistry - November 13, 2020 Category: Chemistry Authors: Julie A. Mund, SuJung Park, Abbi E. Smith, Yongzheng He, Li Jiang, Eric Hawley, Michelle J. Roberson, Dana K. Mitchell, Mohannad Abu-Sultanah, Jin Yuan, Waylan K. Bessler, George Sandusky, Shi Chen, Chi Zhang, Steven D. Rhodes, D. Wade Clapp Tags: Additions and Corrections Source Type: research

Correction: Intermittent enzyme replacement therapy prevents Neu1 deficiency [Additions and Corrections]
VOLUME 295 (2020) PAGES 13556–13569The title of this article was inadvertently swapped with the running title. This error has now been corrected, and the title should read: “Intermittent enzyme replacement therapy with recombinant human β-galactosidase prevents neuraminidase 1 deficiency.” (Source: Journal of Biological Chemistry)
Source: Journal of Biological Chemistry - November 13, 2020 Category: Chemistry Authors: Amanda R. Luu, Cara Wong, Vishal Agrawal, Nathan Wise, Britta Handyside, Melanie J. Lo, Glenn Pacheco, Jessica B. Felix, Alexander Giaramita, Alessandra d'Azzo, Jon Vincelette, Sherry Bullens, Stuart Bunting, Terri M. Christianson, Charles M. Hague, Jonat Tags: Additions and Corrections Source Type: research

Assaying three-dimensional cellular architecture using X-ray tomographic and correlated imaging approaches [Methods and Resources]
Much of our understanding of the spatial organization of and interactions between cellular organelles and macromolecular complexes has been the result of imaging studies utilizing either light- or electron-based microscopic analyses. These classical approaches, while insightful, are nonetheless limited either by restrictions in resolution or by the sheer complexity of generating multidimensional data. Recent advances in the use and application of X-rays to acquire micro- and nanotomographic data sets offer an alternative methodology to visualize cellular architecture at the nanoscale. These new approaches allow for the sub...
Source: Journal of Biological Chemistry - November 13, 2020 Category: Chemistry Authors: Peter O. Bayguinov, Max R. Fisher, James A. J. Fitzpatrick Tags: JBC Reviews Source Type: research

Glycerophosphodiesterase 3 (GDE3) is a lysophosphatidylinositol-specific ectophospholipase C acting as an endocannabinoid signaling switch [Signal Transduction]
Endocannabinoid signaling plays a regulatory role in various (neuro)biological functions. 2-arachidonoylglycerol (2-AG) is the most abundant endocannabinoid, and although its canonical biosynthetic pathway involving phosphoinositide-specific phospholipase C and diacylglycerol lipase α is known, alternative pathways remain unsettled. Here, we characterize a noncanonical pathway implicating glycerophosphodiesterase 3 (GDE3, from GDPD2 gene). Human GDE3 expressed in HEK293T cell membranes catalyzed the conversion of lysophosphatidylinositol (LPI) into monoacylglycerol and inositol-1-phosphate. The enzyme was equally active a...
Source: Journal of Biological Chemistry - November 13, 2020 Category: Chemistry Authors: Fabienne Briand–Mesange, Veronique Pons, Sophie Allart, Julien Masquelier, Gaetan Chicanne, Nicolas Beton, Bernard Payrastre, Giulio G. Muccioli, Jerome Ausseil, Jean–Luc Davignon, Jean–Pierre Salles, Hugues Chap Tags: Lipids Source Type: research

Cadmium-mediated lung injury is exacerbated by the persistence of classically activated macrophages [Bioenergetics]
Heavy metals released into the environment have a significant effect on respiratory health. Lung macrophages are important in mounting an inflammatory response to injury, but they are also involved in repair of injury. Macrophages develop mixed phenotypes in complex pathological conditions and polarize to a predominant phenotype depending on the duration and stage of injury and/or repair. Little is known about the reprogramming required for lung macrophages to switch between these divergent functions; therefore, understanding the mechanism(s) by which macrophages promote metabolic reprogramming to regulate lung injury is e...
Source: Journal of Biological Chemistry - November 13, 2020 Category: Chemistry Authors: Jennifer L. Larson-Casey, Linlin Gu, Oliver Fiehn, A. Brent Carter Tags: Metabolism Source Type: research

O-Fucosylation of ADAMTSL2 is required for secretion and is impacted by geleophysic dysplasia-causing mutations [Molecular Bases of Disease]
ADAMTSL2 mutations cause an autosomal recessive connective tissue disorder, geleophysic dysplasia 1 (GPHYSD1), which is characterized by short stature, small hands and feet, and cardiac defects. ADAMTSL2 is a matricellular protein previously shown to interact with latent transforming growth factor-β binding protein 1 and influence assembly of fibrillin 1 microfibrils. ADAMTSL2 contains seven thrombospondin type-1 repeats (TSRs), six of which contain the consensus sequence for O-fucosylation by protein O-fucosyltransferase 2 (POFUT2). O-fucose–modified TSRs are subsequently elongated to a glucose β1-3-fucose (GlcFuc) di...
Source: Journal of Biological Chemistry - November 13, 2020 Category: Chemistry Authors: Ao Zhang, Steven J. Berardinelli, Christina Leonhard-Melief, Deepika Vasudevan, Ta-Wei Liu, Andrew Taibi, Sharee Giannone, Suneel S. Apte, Bernadette C. Holdener, Robert S. Haltiwanger Tags: Glycobiology and Extracellular Matrices Source Type: research

Interactions of ferritin with scavenger receptor class A members [Protein Structure and Folding]
Scavenger receptors are a superfamily of membrane-bound receptors that recognize both self and nonself targets. Scavenger receptor class A (SR-A) has five known members (SCARA1 to -5 or SR-A1 to -A5), which are type II transmembrane proteins that form homotrimers on the cell surface. SR-A members recognize various ligands and are involved in multiple biological pathways. Among them, SCARA5 can function as a ferritin receptor; however, the interaction between SCARA5 and ferritin has not been fully characterized. Here, we determine the crystal structures of the C-terminal scavenger receptor cysteine-rich (SRCR) domain of bot...
Source: Journal of Biological Chemistry - November 13, 2020 Category: Chemistry Authors: Bowen Yu, Chen Cheng, Yichun Wu, Luqiang Guo, Dandan Kong, Ze Zhang, Yuanyuan Wang, Enlin Zheng, Yingbin Liu, Yongning He Tags: Molecular Biophysics Source Type: research

Obesity-associated microbiota contributes to mucus layer defects in genetically obese mice [Metabolism]
The intestinal mucus layer is a physical barrier separating the tremendous number of gut bacteria from the host epithelium. Defects in the mucus layer have been linked to metabolic diseases, but previous studies predominantly investigated mucus function during high-caloric/low-fiber dietary interventions, thus making it difficult to separate effects mediated directly through diet quality from potential obesity-dependent effects. As such, we decided to examine mucus function in mouse models with metabolic disease to distinguish these factors. Here we show that, in contrast to their lean littermates, genetically obese (ob/ob...
Source: Journal of Biological Chemistry - November 13, 2020 Category: Chemistry Authors: Bȷoern O. Schroeder, George M. H. Birchenough, Meenakshi Pradhan, Elisabeth E. L. Nystrom, Marcus Henricsson, Gunnar C. Hansson, Fredrik Backhed Tags: Microbiology Source Type: research

Small molecule strategies to harness the unfolded protein response: where do we go from here? [Cell Biology]
The unfolded protein response (UPR) plays a central role in regulating endoplasmic reticulum (ER) and global cellular physiology in response to pathologic ER stress. The UPR is comprised of three signaling pathways activated downstream of the ER membrane proteins IRE1, ATF6, and PERK. Once activated, these proteins initiate transcriptional and translational signaling that functions to alleviate ER stress, adapt cellular physiology, and dictate cell fate. Imbalances in UPR signaling are implicated in the pathogenesis of numerous, etiologically-diverse diseases, including many neurodegenerative diseases, protein misfolding d...
Source: Journal of Biological Chemistry - November 13, 2020 Category: Chemistry Authors: Julia M. D. Grandjean, R. Luke Wiseman Tags: JBC Reviews Source Type: research

An automated, high-throughput methodology optimized for quantitative cell-free mitochondrial and nuclear DNA isolation from plasma [DNA and Chromosomes]
Progress in the study of circulating, cell-free nuclear DNA (ccf-nDNA) in cancer detection has led to the development of noninvasive clinical diagnostic tests and has accelerated the evaluation of ccf-nDNA abundance as a disease biomarker. Likewise, circulating, cell-free mitochondrial DNA (ccf-mtDNA) is under similar investigation. However, optimal ccf-mtDNA isolation parameters have not been established, and inconsistent protocols for ccf-nDNA collection, storage, and analysis have hindered its clinical utility. Until now, no studies have established a method for high-throughput isolation that considers both ccf-nDNA and...
Source: Journal of Biological Chemistry - November 13, 2020 Category: Chemistry Authors: Sarah A. Ware, Nikita Desai, Mabel Lopez, Daniel Leach, Yingze Zhang, Luca Giordano, Mehdi Nouraie, Martin Picard, Brett A. Kaufman Tags: Cell Biology Source Type: research

Astrocyte-specific deletion of the transcription factor Yin Yang 1 in murine substantia nigra mitigates manganese-induced dopaminergic neurotoxicity [Molecular Bases of Disease]
Manganese (Mn)-induced neurotoxicity resembles Parkinson's disease (PD), but the mechanisms underpinning its effects remain unknown. Mn dysregulates astrocytic glutamate transporters, GLT-1 and GLAST, and dopaminergic function, including tyrosine hydroxylase (TH). Our previous in vitro studies have shown that Mn repressed GLAST and GLT-1 via activation of transcription factor Yin Yang 1 (YY1). Here, we investigated if in vivo astrocytic YY1 deletion mitigates Mn-induced dopaminergic neurotoxicity, attenuating Mn-induced reduction in GLAST/GLT-1 expression in murine substantia nigra (SN). AAV5-GFAP-Cre-GFP particles were in...
Source: Journal of Biological Chemistry - November 13, 2020 Category: Chemistry Authors: Edward Pajarillo, James Johnson Jr., Asha Rizor, Ivan Nyarko-Danquah, Getinet Adinew, Julia Bornhorst, Michael Stiboller, Tania Schwerdtle, Deok-Soo Son, Michael Aschner, Eunsook Lee Tags: Molecular Bases of Disease Source Type: research

A proton-coupled folate transporter mutation causing hereditary folate malabsorption locks the protein in an inward-open conformation [Molecular Bases of Disease]
The proton-coupled folate transporter (PCFT, SLC46A1) is required for folate intestinal absorption and transport across the choroid plexus. Recent work has identified a F392V mutation causing hereditary folate malabsorption. However, the residue properties responsible for this loss of function remains unknown. Using site-directed mutagenesis, we observed complete loss of function with charged (Lys, Asp, and Glu) and polar (Thr, Ser, and Gln) Phe-392 substitutions and minimal function with some neutral substitutions; however, F392M retained full function. Using the substituted-cysteine accessibility method (with N-biotinyl ...
Source: Journal of Biological Chemistry - November 13, 2020 Category: Chemistry Authors: He-Qin Zhan, Mitra Najmi, Kai Lin, Srinivas Aluri, Andras Fiser, I. David Goldman, Rongbao Zhao Tags: Molecular Bases of Disease Source Type: research

Actin-binding protein profilin1 promotes aggressiveness of clear-cell renal cell carcinoma cells [Molecular Bases of Disease]
Clear-cell renal cell carcinoma (ccRCC), the most common subtype of renal cancer, has a poor clinical outcome. A hallmark of ccRCC is genetic loss-of-function of VHL (von Hippel–Lindau) that leads to a highly vascularized tumor microenvironment. Although many ccRCC patients initially respond to antiangiogenic therapies, virtually all develop progressive, drug-refractory disease. Given the role of dysregulated expressions of cytoskeletal and cytoskeleton-regulatory proteins in tumor progression, we performed analyses of The Cancer Genome Atlas (TCGA) transcriptome data for different classes of actin-binding proteins to de...
Source: Journal of Biological Chemistry - November 13, 2020 Category: Chemistry Authors: Abigail Allen, David Gau, Paul Francoeur, Jordan Sturm, Yue Wang, Ryan Martin, Jodi Maranchie, Anette Duensing, Adam Kaczorowski, Stefan Duensing, Lily Wu, Michael T. Lotze, David Koes, Walter J. Storkus, Partha Roy Tags: Cell Biology Source Type: research

The central domain of cardiac ryanodine receptor governs channel activation, regulation, and stability [Molecular Bases of Disease]
Structural analyses identified the central domain of ryanodine receptor (RyR) as a transducer converting conformational changes in the cytoplasmic platform to the RyR gate. The central domain is also a regulatory hub encompassing the Ca2+-, ATP-, and caffeine-binding sites. However, the role of the central domain in RyR activation and regulation has yet to be defined. Here, we mutated five residues that form the Ca2+ activation site and 10 residues with negatively charged or oxygen-containing side chains near the Ca2+ activation site. We also generated eight disease-associated mutations within the central domain of RyR2. W...
Source: Journal of Biological Chemistry - November 13, 2020 Category: Chemistry Authors: Wenting Guo, Bo Sun, John Paul Estillore, Ruiwu Wang, S. R. Wayne Chen Tags: Membrane Biology Source Type: research