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712 results on '"Vandenberg, Robert"'

212. Identification of a 3rd Na+ Binding Site of the Glycine Transporter, GlyT2.

Author

Subramanian, Nandhitha, Scopelitti, Amanda J., Carland, Jane E., Ryan, Renae M., O’Mara, Megan L., and Vandenberg, Robert J.

Subjects
BINDING sites, GLYCINE, NEURAL transmission, DROSOPHILA, PROTEIN structure
Abstract

The Na+/Cl- dependent glycine transporters GlyT1 and GlyT2 regulate synaptic glycine concentrations. Glycine transport by GlyT2 is coupled to the co-transport of three Na+ ions, whereas transport by GlyT1 is coupled to the co-transport of only two Na+ ions. These differences in ion-flux coupling determine their respective concentrating capacities and have a direct bearing on their functional roles in synaptic transmission. The crystal structures of the closely related bacterial Na+-dependent leucine transporter, LeuTAa, and the Drosophila dopamine transporter, dDAT, have allowed prediction of two Na+ binding sites in GlyT2, but the physical location of the third Na+ site in GlyT2 is unknown. A bacterial betaine transporter, BetP, has also been crystallized and shows structural similarity to LeuTAa. Although betaine transport by BetP is coupled to the co-transport of two Na+ ions, the first Na+ site is not conserved between BetP and LeuTAa, the so called Na1' site. We hypothesized that the third Na+ binding site (Na3 site) of GlyT2 corresponds to the BetP Na1' binding site. To identify the Na3 binding site of GlyT2, we performed molecular dynamics (MD) simulations. Surprisingly, a Na+ placed at the location consistent with the Na1' site of BetP spontaneously dissociated from its initial location and bound instead to a novel Na3 site. Using a combination of MD simulations of a comparative model of GlyT2 together with an analysis of the functional properties of wild type and mutant GlyTs we have identified an electrostatically favorable novel third Na+ binding site in GlyT2 formed by Trp263 and Met276 in TM3, Ala481 in TM6 and Glu648 in TM10. [ABSTRACT FROM AUTHOR]

Published
2016
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213. Dynamics of Forward and Reverse Transport by the Glial Glycine Transporter, Glyt1b

Author

Aubrey, Karin R., Vandenberg, Robert J., Clements, John D., Aubrey, Karin R., Vandenberg, Robert J., and Clements, John D.

Abstract

Glycine is a coagonist at the N-methyl-D-aspartate receptor. Changes in extracellular glycine concentration may modulate N-methyl-D-aspartate receptor function and excitatory synaptic transmission. The GLYT1 glycine transporter is present in glia surrounding excitatory synapses, and plays a key role in regulating extracellular glycine concentration. We investigated the kinetic and other biophysical properties of GLYT1b, stably expressed in CHO cells, using whole-cell patch-clamp techniques. Application of glycine produced an inward current, which decayed within a few seconds to a steady-state level. When glycine was removed, a transient outward current was observed, consistent with reverse transport of accumulated glycine. The outward current was enhanced by elevating intracellular or lowering extracellular [Na(+)], and was modulated by changes in extracellular [glycine] and time of glycine application. We developed a model of GLYT1b function, which accurately describes the time course of the transporter current under a range of experimental conditions. The model predicts that glial uptake of glycine will decay toward zero during a sustained period of elevated glycine concentration. This property of GLYT1b may permit spillover from glycinergic terminals to nearby excitatory terminals during a prolonged burst of inhibitory activity, and reverse transport may extend the period of elevated glycine concentration beyond the end of the inhibitory burst.

Published
2005

224. Longitudinal Research: A Panel Discussion on Conceptual Issues, Research Design, and Statistical Techniques

Author

Wang, Mo, Beal, Daniel J., Chan, David, Newman, Daniel A., Vancouver, Jeffrey B., and Vandenberg, Robert J.

Abstract

The goal of this article is to clarify the conceptual, methodological, and practical issues that frequently emerge when conducting longitudinal research, as well as in the journal review process. Using a panel discussion format, the current authors address 13 questions associated with 3 aspects of longitudinal research: conceptual issues, research design, and statistical techniques. These questions are intentionally framed at a general level so that the authors could address them from their diverse perspectives. The authors’ perspectives and recommendations provide a useful guide for conducting and reviewing longitudinal studies in work, aging, and retirement research.

Published
2017
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249. Developing GIS Tools to Meet the Needs of Spatially Distributed Assets – Integrating Field GPS measurements, Photos, Inspections and Risk Analysis for Waterways Asset Management using ArcPAD, ArcMAP, Geodatabase and Maximo 7.1

Author

Hassy, Kurt, primary, Vandenberg, Robert, additional, Sen, Dipankar, additional, Drury, Ed, additional, Adeeb, Neddal Ali, additional, Berggren, John, additional, Chan, Kirsten, additional, and Bernhard, Jill, additional

Published
2010
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