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Articles 1 - 15 of 15
Full-Text Articles in Life Sciences
Calcium's Role As Nuanced Modulator Of Cellular Physiology In The Brain, Hilaree N. Frazier, Shaniya Maimaiti, Katie L. Anderson, Lawrence D. Brewer, John C. Gant, Nada M. Porter, Olivier Thibault
Calcium's Role As Nuanced Modulator Of Cellular Physiology In The Brain, Hilaree N. Frazier, Shaniya Maimaiti, Katie L. Anderson, Lawrence D. Brewer, John C. Gant, Nada M. Porter, Olivier Thibault
Pharmacology and Nutritional Sciences Faculty Publications
Neuroscientists studying normal brain aging, spinal cord injury, Alzheimer’s disease (AD) and other neurodegenerative diseases have focused considerable effort on carefully characterizing intracellular perturbations in calcium dynamics or levels. At the cellular level, calcium is known for controlling life and death and orchestrating most events in between. For many years, intracellular calcium has been recognized as an essential ion associated with nearly all cellular functions from cell growth to degeneration. Often the emphasis is on the negative impact of calcium dysregulation and the typical worse-case-scenario leading inevitably to cell death. However, even high amplitude calcium transients, when executed acutely can …
Oled Loki As A Catalyst For Tertiary Amine And Hydroxamate Glycosylation, Ryan R. Hughes, Khaled A. Shaaban, Jianjun Zhang, Hongnan Cao, George N. Phillips Jr., Jon S. Thorson
Oled Loki As A Catalyst For Tertiary Amine And Hydroxamate Glycosylation, Ryan R. Hughes, Khaled A. Shaaban, Jianjun Zhang, Hongnan Cao, George N. Phillips Jr., Jon S. Thorson
Center for Pharmaceutical Research and Innovation Faculty Publications
We describe the ability of an engineered glycosyltransferase (OleD Loki) to catalyze the N‐glycosylation of tertiary‐amine‐containing drugs and trichostatin hydroxamate glycosyl ester formation. As such, this study highlights the first bacterial model catalyst for tertiary‐amine N‐glycosylation and further expands the substrate scope and synthetic potential of engineered OleDs. In addition, this work could open the door to the discovery of similar capabilities among other permissive bacterial glycosyltransferases.
Dauer Larva Quiescence Alters The Circuitry Of Microrna Pathways Regulating Cell Fate Progression In C. Elegans, Xantha Karp, Victor Ambros
Dauer Larva Quiescence Alters The Circuitry Of Microrna Pathways Regulating Cell Fate Progression In C. Elegans, Xantha Karp, Victor Ambros
Victor R. Ambros
In C. elegans larvae, the execution of stage-specific developmental events is controlled by heterochronic genes, which include those encoding a set of transcription factors and the microRNAs that regulate the timing of their expression. Under adverse environmental conditions, developing larvae enter a stress-resistant, quiescent stage called 'dauer'. Dauer larvae are characterized by the arrest of all progenitor cell lineages at a stage equivalent to the end of the second larval stage (L2). If dauer larvae encounter conditions favorable for resumption of reproductive growth, they recover and complete development normally, indicating that post-dauer larvae possess mechanisms to accommodate an indefinite period …
The Gating Charge Should Not Be Estimated By Fitting A Two-State Model To A Q-V Curve, Francisco Bezanilla, Carlos A. Villalba-Galea
The Gating Charge Should Not Be Estimated By Fitting A Two-State Model To A Q-V Curve, Francisco Bezanilla, Carlos A. Villalba-Galea
School of Pharmacy Faculty Articles
The voltage dependence of charges in voltage-sensitive proteins, typically displayed as charge versus voltage (Q-V) curves, is often quantified by fitting it to a simple two-state Boltzmann function. This procedure overlooks the fact that the fitted parameters, including the total charge, may be incorrect if the charge is moving in multiple steps. We present here the derivation of a general formulation for Q-V curves from multistate sequential models, including the case of infinite number of states. We demonstrate that the commonly used method to estimate the charge per molecule using a simple Boltzmann fit is not only inadequate, but in …
Sensing Charges Of The Ciona Intestinalis Voltage-Sensing Phosphatase, Carlos A. Villalba-Galea, Ludivine Frezza, Walter Sandtner, Francisco Bezanilla
Sensing Charges Of The Ciona Intestinalis Voltage-Sensing Phosphatase, Carlos A. Villalba-Galea, Ludivine Frezza, Walter Sandtner, Francisco Bezanilla
School of Pharmacy Faculty Articles
Voltage control over enzymatic activity in voltage-sensitive phosphatases (VSPs) is conferred by a voltage-sensing domain (VSD) located in the N terminus. These VSDs are constituted by four putative transmembrane segments (S1 to S4) resembling those found in voltage-gated ion channels. The putative fourth segment (S4) of the VSD contains positive residues that likely function as voltage-sensing elements. To study in detail how these residues sense the plasma membrane potential, we have focused on five arginines in the S4 segment of the Ciona intestinalis VSP (Ci-VSP). After implementing a histidine scan, here we show that four arginine-to-histidine mutants, namely R223H to …
36 Degrees Step Size Of Proton-Driven C-Ring Rotation In Fof1-Atp Synthase, Monika Düser, Nawid Zarrabi, Daniel Cipriano, Stefan Ernst, Gary Glick, Stanley Dunn, Michael Börsch
36 Degrees Step Size Of Proton-Driven C-Ring Rotation In Fof1-Atp Synthase, Monika Düser, Nawid Zarrabi, Daniel Cipriano, Stefan Ernst, Gary Glick, Stanley Dunn, Michael Börsch
Stanley D Dunn
Synthesis of adenosine triphosphate ATP, the 'biological energy currency', is accomplished by F(o)F(1)-ATP synthase. In the plasma membrane of Escherichia coli, proton-driven rotation of a ring of 10 c subunits in the F(o) motor powers catalysis in the F(1) motor. Although F(1) uses 120 degrees stepping during ATP synthesis, models of F(o) predict either an incremental rotation of c subunits in 36 degrees steps or larger step sizes comprising several fast substeps. Using single-molecule fluorescence resonance energy transfer, we provide the first experimental determination of a 36 degrees sequential stepping mode of the c-ring during ATP synthesis.
Structural Basis For Activation Of Calcineurin By Calmodulin, Julie Rumi-Masante, Farai I. Rusinga, Terrence E. Lester, Tori B. Dunlap, Todd D. Williams, A. Keith Dunker, David D. Weis, Trevor P. Creamer
Structural Basis For Activation Of Calcineurin By Calmodulin, Julie Rumi-Masante, Farai I. Rusinga, Terrence E. Lester, Tori B. Dunlap, Todd D. Williams, A. Keith Dunker, David D. Weis, Trevor P. Creamer
Center for Structural Biology Faculty Publications
The highly conserved phosphatase calcineurin (CaN) plays vital roles in numerous processes including T-cell activation, development and function of the central nervous system, and cardiac growth. It is activated by the calcium sensor calmodulin (CaM). CaM binds to a regulatory domain (RD) within CaN, causing a conformational change that displaces an autoinhibitory domain (AID) from the active site, resulting in activation of the phosphatase. This is the same general mechanism by which CaM activates CaM-dependent protein kinases. Previously published data have hinted that the RD of CaN is intrinsically disordered. In this work, we demonstrate that the RD is unstructured …
Usp8 Promotes Smoothened Signaling By Preventing Its Ubiquitination And Changing Its Subcellular Localization, Ruohan Xia, Hongge Jia, Junkai Fan, Yajuan Liu, Jianhang Jia
Usp8 Promotes Smoothened Signaling By Preventing Its Ubiquitination And Changing Its Subcellular Localization, Ruohan Xia, Hongge Jia, Junkai Fan, Yajuan Liu, Jianhang Jia
Molecular and Cellular Biochemistry Faculty Publications
The seven transmembrane protein Smoothened (Smo) is a critical component of the Hedgehog (Hh) signaling pathway and is regulated by phosphorylation, dimerization, and cell-surface accumulation upon Hh stimulation. However, it is not clear how Hh regulates Smo accumulation on the cell surface or how Hh regulates the intracellular trafficking of Smo. In addition, little is known about whether ubiquitination is involved in Smo regulation. In this study, we demonstrate that Smo is multi-monoubiquitinated and that Smo ubiquitination is inhibited by Hh and by phosphorylation. Using an in vivo RNAi screen, we identified ubiquitin-specific protease 8 (USP8) as a deubiquitinase that …
Juvenile Hormone Regulates Vitellogenin Gene Expression Through Insulin-Like Peptide Signaling Pathway In The Red Flour Beetle, Tribolium Castaneum, Zhentao Sheng, Jingjing Xu, Hua Bai, Fang Zhu, Subba R. Palli
Juvenile Hormone Regulates Vitellogenin Gene Expression Through Insulin-Like Peptide Signaling Pathway In The Red Flour Beetle, Tribolium Castaneum, Zhentao Sheng, Jingjing Xu, Hua Bai, Fang Zhu, Subba R. Palli
Entomology Faculty Publications
Our recent studies identified juvenile hormone (JH) and nutrition as the two key signals that regulate vitellogenin (Vg) gene expression in the red flour beetle, Tribolium castaneum. Juvenile hormone regulation of Vg synthesis has been known for a long time in several insects, but the mechanism of JH action is not known. Experiments were conducted to determine the mechanism of action of these two signals in regulation of Vg gene expression. Injection of bovine insulin or FOXO double-stranded RNA into the previtellogenic, starved, or JH-deficient female adults increased Vg mRNA and protein levels, thereby implicating the pivotal role for …
Systematic Two-Hybrid And Comparative Proteomic Analyses Reveal Novel Yeast Pre-Mrna Splicing Factors Connected To Prp19, Liping Ren, Janel R. Mclean, Tony R. Hazbun, Stanley Fields, Craig Vander Kooi, Melanie D. Ohi, Kathleen L. Gould
Systematic Two-Hybrid And Comparative Proteomic Analyses Reveal Novel Yeast Pre-Mrna Splicing Factors Connected To Prp19, Liping Ren, Janel R. Mclean, Tony R. Hazbun, Stanley Fields, Craig Vander Kooi, Melanie D. Ohi, Kathleen L. Gould
Molecular and Cellular Biochemistry Faculty Publications
Prp19 is the founding member of the NineTeen Complex, or NTC, which is a spliceosomal subcomplex essential for spliceosome activation. To define Prp19 connectivity and dynamic protein interactions within the spliceosome, we systematically queried the Saccharomyces cerevisiae proteome for Prp19 WD40 domain interaction partners by two-hybrid analysis. We report that in addition to S. cerevisiae Cwc2, the splicing factor Prp17 binds directly to the Prp19 WD40 domain in a 1:1 ratio. Prp17 binds simultaneously with Cwc2 indicating that it is part of the core NTC complex. We also find that the previously uncharacterized protein Urn1 (Dre4 in Schizosaccharomyces pombe) directly …
Mechanism Of N-Methylation By The Trna M1g37 Methyltransferase Trm5., Thomas Christian, Georges Lahoud, Cuiping Liu, Katherine Hoffmann, John J Perona, Ya-Ming Hou
Mechanism Of N-Methylation By The Trna M1g37 Methyltransferase Trm5., Thomas Christian, Georges Lahoud, Cuiping Liu, Katherine Hoffmann, John J Perona, Ya-Ming Hou
Department of Biochemistry and Molecular Biology Faculty Papers
Trm5 is a eukaryal and archaeal tRNA methyltransferase that catalyzes methyl transfer from S-adenosylmethionine (AdoMet) to the N(1) position of G37 directly 3' to the anticodon. While the biological role of m(1)G37 in enhancing translational fidelity is well established, the catalytic mechanism of Trm5 has remained obscure. To address the mechanism of Trm5 and more broadly the mechanism of N-methylation to nucleobases, we examined the pH-activity profile of an archaeal Trm5 enzyme, and performed structure-guided mutational analysis. The data reveal a marked dependence of enzyme-catalyzed methyl transfer on hydrogen ion equilibria: the single-turnover rate constant for methylation increases by one …
A Feedback Circuit Involving Let-7-Family Mirnas And Daf-12 Integrates Environmental Signals And Developmental Timing In Caenorhabditis Elegans, Christopher M. Hammell, Xantha Karp, Victor R. Ambros
A Feedback Circuit Involving Let-7-Family Mirnas And Daf-12 Integrates Environmental Signals And Developmental Timing In Caenorhabditis Elegans, Christopher M. Hammell, Xantha Karp, Victor R. Ambros
Victor R. Ambros
Animal development is remarkably robust; cell fates are specified with spatial and temporal precision despite physiological and environmental contingencies. Favorable conditions cause Caenorhabditis elegans to develop rapidly through four larval stages (L1-L4) to the reproductive adult. In unfavorable conditions, L2 larvae can enter the developmentally quiescent, stress-resistant dauer larva stage, enabling them to survive for prolonged periods before completing development. A specific progression of cell division and differentiation events occurs with fidelity during the larval stages, regardless of whether an animal undergoes continuous or dauer-interrupted development. The temporal patterning of developmental events is controlled by the heterochronic genes, whose products …
The Leishmania Donovani Lipophosphoglycan Excludes The Vesicular Proton-Atpase From Phagosomes By Impairing The Recruitment Of Synaptotagmin V, Adrien F. Vinet, Mitsunori Fukuda, Salvatore J. Turco, Albert Descoteaux
The Leishmania Donovani Lipophosphoglycan Excludes The Vesicular Proton-Atpase From Phagosomes By Impairing The Recruitment Of Synaptotagmin V, Adrien F. Vinet, Mitsunori Fukuda, Salvatore J. Turco, Albert Descoteaux
Molecular and Cellular Biochemistry Faculty Publications
We recently showed that the exocytosis regulator Synaptotagmin (Syt) V is recruited to the nascent phagosome and remains associated throughout the maturation process. In this study, we investigated the possibility that Syt V plays a role in regulating interactions between the phagosome and the endocytic organelles. Silencing of Syt V by RNA interference revealed that Syt V contributes to phagolysosome biogenesis by regulating the acquisition of cathepsin D and the vesicular proton-ATPase. In contrast, recruitment of cathepsin B, the early endosomal marker EEA1 and the lysosomal marker LAMP1 to phagosomes was normal in the absence of Syt V. As Leishmania …
Polyglutamine Disruption Of The Huntingtin Exon 1 N Terminus Triggers A Complex Aggregation Mechanism, Ashwani K. Thakur, Murali Jayaraman, Rakesh Mishra, Monika Thakur, Veronique M. Chellgren, In-Ja L Byeon, Dalaver H. Anjum, Ravindra Kodali, Trevor P. Creamer, James F. Conway, Angela M. Gronenborn, Ronald Wetzel
Polyglutamine Disruption Of The Huntingtin Exon 1 N Terminus Triggers A Complex Aggregation Mechanism, Ashwani K. Thakur, Murali Jayaraman, Rakesh Mishra, Monika Thakur, Veronique M. Chellgren, In-Ja L Byeon, Dalaver H. Anjum, Ravindra Kodali, Trevor P. Creamer, James F. Conway, Angela M. Gronenborn, Ronald Wetzel
Molecular and Cellular Biochemistry Faculty Publications
Simple polyglutamine (polyQ) peptides aggregate in vitro via a nucleated growth pathway directly yielding amyloid-like aggregates. We show here that the 17-amino-acid flanking sequence (HTTNT) N-terminal to the polyQ in the toxic huntingtin exon 1 fragment imparts onto this peptide a complex alternative aggregation mechanism. In isolation, the HTTNT peptide is a compact coil that resists aggregation. When polyQ is fused to this sequence, it induces in HTTNT, in a repeat-length dependent fashion, a more extended conformation that greatly enhances its aggregation into globular oligomers with HTTNT cores and exposed polyQ. In a second …
Compartmental Specificity Of Cellular Membrane Fusion Encoded In Snare Proteins, James Mcnew, Frank Parlati, Ryorichi Fukuda, Robert Johnston, Keren Paz, Fabienne Paumet, Thomas Sollner, James Rothman
Compartmental Specificity Of Cellular Membrane Fusion Encoded In Snare Proteins, James Mcnew, Frank Parlati, Ryorichi Fukuda, Robert Johnston, Keren Paz, Fabienne Paumet, Thomas Sollner, James Rothman
Fabienne Paumet
No abstract provided.