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380 results on '"Forrest, Lucy R."'

3. Intestinal serotonin and fluoxetine exposure modulate bacterial colonization in the gut

Author

Fung, Thomas C, Vuong, Helen E, Luna, Cristopher DG, Pronovost, Geoffrey N, Aleksandrova, Antoniya A, Riley, Noah G, Vavilina, Anastasia, McGinn, Julianne, Rendon, Tomiko, Forrest, Lucy R, and Hsiao, Elaine Y

Subjects
Microbiology, Biological Sciences, Genetics, Prevention, Depression, Digestive Diseases, Nutrition, Mental Health, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Underpinning research, Aetiology, Oral and gastrointestinal, Infection, Administration, Oral, Animals, Bacteria, Feces, Female, Firmicutes, Fluoxetine, Gastrointestinal Microbiome, Genetic Variation, Host Microbial Interactions, Intestines, Male, Mice, Mice, Inbred C57BL, Serotonin, Serotonin Receptor Agonists, Selective Serotonin Reuptake Inhibitors, Specific Pathogen-Free Organisms, Medical Microbiology
Abstract

The gut microbiota regulates levels of serotonin (5-hydroxytryptamine (5-HT)) in the intestinal epithelium and lumen1-5. However, whether 5-HT plays a functional role in bacteria from the gut microbiota remains unknown. We demonstrate that elevating levels of intestinal lumenal 5-HT by oral supplementation or genetic deficiency in the host 5-HT transporter (SERT) increases the relative abundance of spore-forming members of the gut microbiota, which were previously reported to promote host 5-HT biosynthesis. Within this microbial community, we identify Turicibacter sanguinis as a gut bacterium that expresses a neurotransmitter sodium symporter-related protein with sequence and structural homology to mammalian SERT. T. sanguinis imports 5-HT through a mechanism that is inhibited by the selective 5-HT reuptake inhibitor fluoxetine. 5-HT reduces the expression of sporulation factors and membrane transporters in T. sanguinis, which is reversed by fluoxetine exposure. Treating T. sanguinis with 5-HT or fluoxetine modulates its competitive colonization in the gastrointestinal tract of antibiotic-treated mice. In addition, fluoxetine reduces the membership of T. sanguinis in the gut microbiota of conventionally colonized mice. Host association with T. sanguinis alters intestinal expression of multiple gene pathways, including those important for lipid and steroid metabolism, with corresponding reductions in host systemic triglyceride levels and inguinal adipocyte size. Together, these findings support the notion that select bacteria indigenous to the gut microbiota signal bidirectionally with the host serotonergic system to promote their fitness in the intestine.

Published
2019

18. Membrane Protein Simulations: Modelling a Complex Environment

Author

Bond, Peter J., Cuthbertson, Jonathan, Deol, Sundeep S., Forrest, Lucy R., Johnston, Jennifer, Patargias, George, Sansom, Mark S.P., Barth, Timothy J., editor, Griebel, Michael, editor, Keyes, David E., editor, Nieminen, Risto M., editor, Roose, Dirk, editor, Schlick, Tamar, editor, Leimkuhler, Benedict, editor, Chipot, Christophe, editor, Elber, Ron, editor, Laaksonen, Aatto, editor, Mark, Alan, editor, Schütte, Christoph, editor, and Skeel, Robert, editor

Published
2006
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20. Osmotic stress response in BetP: How lipids and K+ team up to overcome downregulation

Author

Heinz, Veronika, primary, Gueler, Guennur, additional, Leone, Vanessa, additional, Madej, M. Gregor, additional, Maksimov, Stanislav, additional, Gaertner, Rebecca M., additional, Rudi, Olga, additional, Hamdi, Farzad, additional, Kastritis, Panagiotis L., additional, Maentele, Werner, additional, Kraemer, Reinhard, additional, Forrest, Lucy R., additional, Perez, Camilo, additional, and Ziegler, Christine, additional

Published
2022
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27. Interpreting hydrogen-deuterium exchange experiments with molecular simulations: Tutorials and applications of the HDXer ensemble reweighting software [Article v1.0]

Author

Lee, Paul Suhwan, primary, Bradshaw, Richard T., additional, Marinelli, Fabrizio, additional, Kihn, Kyle, additional, Smith, Ally, additional, Wintrode, Patrick L., additional, Deredge, Daniel J., additional, Faraldo-Gómez, José D., additional, and Forrest, Lucy R., additional

Published
2022
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40. On the Role of a Conserved Methionine in the Na+-Coupling Mechanism of a Neurotransmitter Transporter Homolog.

Author

Zhou, Wenchang, Trinco, Gianluca, Slotboom, Dirk J., Forrest, Lucy R., and Faraldo-Gómez, José D.

Subjects
EXCITATORY amino acids, CHEMICAL kinetics, ORGANIC cation transporters
Abstract

Excitatory amino acid transporters (EAAT) play a key role in glutamatergic synaptic communication. Driven by transmembrane cation gradients, these transporters catalyze the reuptake of glutamate from the synaptic cleft once this neurotransmitter has been utilized for signaling. Two decades ago, pioneering studies in the Kanner lab identified a conserved methionine within the transmembrane domain as key for substrate turnover rate and specificity; later structural work, particularly for the prokaryotic homologs GltPh and GltTk, revealed that this methionine is involved in the coordination of one of the three Na+ ions that are co-transported with the substrate. Albeit extremely atypical, the existence of this interaction is consistent with biophysical analyses of GltPh showing that mutations of this methionine diminish the binding cooperativity between substrates and Na+. It has been unclear, however, whether this intriguing methionine influences the thermodynamics of the transport reaction, i.e., its substrate:ion stoichiometry, or whether it simply fosters a specific kinetics in the binding reaction, which, while influential for the turnover rate, do not fundamentally explain the ion-coupling mechanism of this class of transporters. Here, studies of GltTk using experimental and computational methods independently arrive at the conclusion that the latter hypothesis is the most plausible, and lay the groundwork for future efforts to uncover the underlying mechanism. [ABSTRACT FROM AUTHOR]

Published
2022
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