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Article ; Online: Direct and indirect mechanisms by which the gut microbiota influence host serotonin systems.

Legan, Theresa B / Lavoie, Brigitte / Mawe, Gary M

2022 Volume 34, Issue 10, Page(s) e14346

Abstract: Mounting evidence highlights the pivotal role of enteric microbes as a dynamic interface with the host. Indeed, the gut microbiota, located in the lumen of the gastrointestinal (GI) tract, influence many essential physiological processes that are evident ...

Abstract	Mounting evidence highlights the pivotal role of enteric microbes as a dynamic interface with the host. Indeed, the gut microbiota, located in the lumen of the gastrointestinal (GI) tract, influence many essential physiological processes that are evident in both healthy and pathological states. A key signaling molecule throughout the body is serotonin (5-hydroxytryptamine; 5-HT), which acts in the GI tract to regulate numerous gut functions including intestinal motility and secretion. The gut microbiota can modulate host 5-HT systems both directly and indirectly. Direct actions of gut microbes, evidenced by studies using germ-free animals or antibiotic administration, alter the expression of key 5-HT-related genes to promote 5-HT biosynthesis. Indirectly, the gut microbiota produce numerous microbial metabolites, whose actions can influence host serotonergic systems in a variety of ways. This review summarizes the current knowledge regarding mechanisms by which gut bacteria act to regulate host 5-HT and 5-HT-mediated gut functions, as well as implications for 5-HT in the microbiota-gut-brain axis.
MeSH term(s)	Animals ; Anti-Bacterial Agents ; Gastrointestinal Microbiome ; Gastrointestinal Motility/physiology ; Gastrointestinal Tract/metabolism ; Microbiota/physiology ; Serotonin/metabolism
Chemical Substances	Anti-Bacterial Agents ; Serotonin (333DO1RDJY)
Language	English
Publishing date	2022-03-05
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	1186328-6
ISSN	1365-2982 ; 1350-1925
ISSN (online)	1365-2982
ISSN	1350-1925
DOI	10.1111/nmo.14346
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Article: Epithelial 5-HT

Mawe, Gary M / Hurd, Molly / Hennig, Grant W / Lavoie, Brigitte

Advances in experimental medicine and biology

2022 Volume 1383, Page(s) 329–334

Abstract: Because of their importance in the regulation of gut functions, several therapeutic targets involving serotonin-related proteins have been developed or repurposed to treat motility disorders, including serotonin transporter inhibitors, tryptophan ... ...

Abstract	Because of their importance in the regulation of gut functions, several therapeutic targets involving serotonin-related proteins have been developed or repurposed to treat motility disorders, including serotonin transporter inhibitors, tryptophan hydroxylase blockers, 5-HT3 antagonists, and 5-HT4 agonists. This chapter focuses on our discovery of 5-HT4 receptors in the epithelial cells of the colon and our efforts to evaluate the effects of stimulating these receptors. 5-HT4 receptors appear to be expressed by all epithelial cells in the mouse colon, based on expression of a reporter gene driven by the 5-HT4 receptor promoter. Application of 5-HT4 agonists to the mucosal surface causes serotonin release from enterochromaffin cells, mucus secretion from goblet cells, and chloride secretion from enterocytes. Luminal administration of 5-HT4 agonists speeds up colonic motility and suppresses distention-induced nociceptive responses. Luminal administration of 5-HT4 agonists also decreases the development of, and improves recovery from, experimental colitis. Recent studies determined that the prokinetic actions of minimally absorbable 5-HT4 agonists are just as effective as absorbable compounds. Collectively, these findings indicate that targeting epithelial receptors with non-absorbable 5-HT4 agonists could offer a safe and effective strategy for treating constipation and colitis.
MeSH term(s)	Mice ; Animals ; Serotonin/metabolism ; Serotonin 5-HT4 Receptor Agonists/pharmacology ; Serotonin 5-HT4 Receptor Agonists/therapeutic use ; Serotonin 5-HT4 Receptor Agonists/metabolism ; Constipation/drug therapy ; Receptors, Serotonin, 5-HT4/metabolism ; Colon/metabolism ; Colitis/chemically induced ; Colitis/drug therapy ; Inflammation/metabolism ; Gastrointestinal Motility/physiology
Chemical Substances	Serotonin (333DO1RDJY) ; Serotonin 5-HT4 Receptor Agonists ; Receptors, Serotonin, 5-HT4 (158165-40-3)
Language	English
Publishing date	2022-12-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	410187-X
ISSN	0065-2598
ISSN	0065-2598
DOI	10.1007/978-3-031-05843-1_30
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Zs.A 3192: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Protective actions of a luminally acting 5-HT

Hurd, Molly / Haag, Melody M / Kwasnik, Matthew J / Wykosky, Jill / Lavoie, Brigitte / Mawe, Gary M

Neurogastroenterology and motility

2023 Volume 35, Issue 11, Page(s) e14673

Abstract: Background: 5-hydroxytryptamine 4 receptors (5-HT: Methods: The dextran sodium sulfate (DSS), trinitrobenzene sulfonic acid (TNBS), and interleukin 10 knockout (IL-10KO) models of colitis were used to test the protective effects of the luminally ... ...

Abstract	Background: 5-hydroxytryptamine 4 receptors (5-HT Methods: The dextran sodium sulfate (DSS), trinitrobenzene sulfonic acid (TNBS), and interleukin 10 knockout (IL-10KO) models of colitis were used to test the protective effects of the luminally acting 5-HT Key results: Daily enema of 5HT4-LA1 attenuated the development of, and accelerated recovery from, active colitis. Enema administration of 5HT4-LA1 did not attenuate the development of colitis in 5-HT Conclusions and inferences: Luminally restricted 5-HT
MeSH term(s)	Humans ; Mice ; Animals ; Serotonin ; Caco-2 Cells ; Colitis/chemically induced ; Colitis/drug therapy ; Colitis/pathology ; Mice, Knockout ; Water
Chemical Substances	Serotonin (333DO1RDJY) ; Water (059QF0KO0R)
Language	English
Publishing date	2023-10-13
Publishing country	England
Document type	Journal Article
ZDB-ID	1186328-6
ISSN	1365-2982 ; 1350-1925
ISSN (online)	1365-2982
ISSN	1350-1925
DOI	10.1111/nmo.14673
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Article ; Online: Monitoring Gut Epithelium Serotonin and Melatonin Overflow Provides Spatial Mapping of Inflammation.

Perez, Fernando / Kotecha, Nikki / Lavoie, Brigitte / Mawe, Gary M / Patel, Bhavik Anil

Chembiochem : a European journal of chemical biology

2022 Volume 24, Issue 2, Page(s) e202200334

Abstract: Electrochemical arrays were used to measure the overflow of serotonin (5-HT) and melatonin (MEL) from the entire colon of healthy mice and mice with chemical-induced inflammatory bowel disease (IBD), to understand the interplay between inflammation and ... ...

Abstract	Electrochemical arrays were used to measure the overflow of serotonin (5-HT) and melatonin (MEL) from the entire colon of healthy mice and mice with chemical-induced inflammatory bowel disease (IBD), to understand the interplay between inflammation and colonic function. We show that 5-HT overflow is increased, whilst MEL levels are reduced, in inflamed tissues. The levels of MEL are increased at the interface between healthy and inflamed regions within the colon and may limit the spread of inflammation. Understanding the interplay between inflammation and mucosal epithelial signalling can provide key insight into colonic function and aid the development of effective therapeutic strategies to treat gastrointestinal diseases.
MeSH term(s)	Mice ; Animals ; Serotonin ; Melatonin ; Intestinal Mucosa ; Inflammation ; Epithelium
Chemical Substances	Serotonin (333DO1RDJY) ; Melatonin (JL5DK93RCL)
Language	English
Publishing date	2022-12-02
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2020469-3
ISSN	1439-7633 ; 1439-4227
ISSN (online)	1439-7633
ISSN	1439-4227
DOI	10.1002/cbic.202200334
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Article ; Online: Tryptophan-synthesizing bacteria enhance colonic motility.

Legan, Theresa B / Lavoie, Brigitte / Norberg, Emilia / Ley, Isabella C / Tack, Stephanie / Tompkins, Thomas A / Wargo, Matthew J / Mawe, Gary M

Neurogastroenterology and motility

2023 Volume 35, Issue 10, Page(s) e14629

Abstract: Background: An emerging strategy to treat symptoms of gastrointestinal (GI) dysmotility utilizes the administration of isolated bacteria. However, the underlying mechanisms of action of these bacterial agents are not well established. Here, we elucidate ...

Abstract	Background: An emerging strategy to treat symptoms of gastrointestinal (GI) dysmotility utilizes the administration of isolated bacteria. However, the underlying mechanisms of action of these bacterial agents are not well established. Here, we elucidate a novel approach to promote intestinal motility by exploiting the biochemical capability of specific bacteria to produce the serotonin (5-HT) precursor, tryptophan (Trp). Methods: Mice were treated daily for 1 week by oral gavage of Bacillus (B.) subtilis (R0179), heat-inactivated R0179, or a tryptophan synthase-null strain of B. subtilis (1A2). Tissue levels of Trp, 5-HT, and 5-hydroxyindoleacetic acid (5-HIAA) were measured and changes in motility were evaluated. Key results: Mice treated with B. subtilis R0179 exhibited greater colonic tissue levels of Trp and the 5-HT breakdown product, 5-HIAA, compared to vehicle-treated mice. Furthermore, B. subtilis treatment accelerated colonic motility in both healthy mice as well as in a mouse model of constipation. These effects were not observed with heat-inactivated R0179 or the live 1A2 strain that does not express tryptophan synthase. Lastly, we found that the prokinetic effects of B. subtilis R0179 were blocked by coadministration of a 5-HT Conclusions and inferences: Taken together, these data demonstrate that intestinal motility can be augmented by treatment with bacteria that synthesize Trp, possibly through increased 5-HT signaling and/or actions of Trp metabolites, and involvement of the 5-HT
MeSH term(s)	Mice ; Animals ; Tryptophan/pharmacology ; Serotonin/metabolism ; Hydroxyindoleacetic Acid ; Tryptophan Synthase/pharmacology ; Gastrointestinal Motility ; Mice, Knockout ; Bacteria
Chemical Substances	Tryptophan (8DUH1N11BX) ; Serotonin (333DO1RDJY) ; Hydroxyindoleacetic Acid (54-16-0) ; Tryptophan Synthase (EC 4.2.1.20)
Language	English
Publishing date	2023-06-25
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1186328-6
ISSN	1365-2982 ; 1350-1925
ISSN (online)	1365-2982
ISSN	1350-1925
DOI	10.1111/nmo.14629
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Article ; Online: CDK11

Renshaw, Matthew J / Panagiotou, Thomas C / Lavoie, Brigitte D / Wilde, Andrew

The Journal of biological chemistry

2019 Volume 294, Issue 49, Page(s) 18639–18649

Abstract: Rigorous spatiotemporal regulation of cell division is required to maintain genome stability. The final stage in cell division, when the cells physically separate (abscission), is tightly regulated to ensure that it occurs after cytokinetic events such ... ...

Abstract	Rigorous spatiotemporal regulation of cell division is required to maintain genome stability. The final stage in cell division, when the cells physically separate (abscission), is tightly regulated to ensure that it occurs after cytokinetic events such as chromosome segregation. A key regulator of abscission timing is Aurora B kinase activity, which inhibits abscission and forms the major activity of the abscission checkpoint. This checkpoint prevents abscission until chromosomes have been cleared from the cytokinetic machinery. Here we demonstrate that the mitosis-specific CDK11
MeSH term(s)	Aurora Kinase B/genetics ; Aurora Kinase B/metabolism ; Blotting, Western ; Cell Division/genetics ; Cell Division/physiology ; Chromosome Segregation/genetics ; Chromosome Segregation/physiology ; Cyclin-Dependent Kinases/genetics ; Cyclin-Dependent Kinases/metabolism ; Cyclins/genetics ; Cyclins/metabolism ; Cytokinesis/genetics ; Cytokinesis/physiology ; Fluorescent Antibody Technique ; HeLa Cells ; Humans ; Mitosis/genetics ; Mitosis/physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Time-Lapse Imaging
Chemical Substances	CCNL1 protein, human ; Cyclins ; AURKB protein, human (EC 2.7.11.1) ; Aurora Kinase B (EC 2.7.11.1) ; CDK11B protein, human (EC 2.7.11.22) ; Cyclin-Dependent Kinases (EC 2.7.11.22)
Language	English
Publishing date	2019-10-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.RA119.009107
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Article: pRb and condensin--local control of global chromosome structure.

Lavoie, Brigitte D

Genes & development

2008 Volume 22, Issue 8, Page(s) 964–969

Abstract: Rb mutants exhibit aneuploidy and aberrant chromosome structure during mitosis. In this issue of Genes & Development, a new paper from Longworth and colleagues (1011-1024) describes both physical and functional interactions between Drosophila Rbf1 and ... ...

Abstract	Rb mutants exhibit aneuploidy and aberrant chromosome structure during mitosis. In this issue of Genes & Development, a new paper from Longworth and colleagues (1011-1024) describes both physical and functional interactions between Drosophila Rbf1 and the dCAP-D3 subunit of condensin II. This work directly implicates the Rb family proteins in mitotic chromosome condensation and suggests that a failure in targeting condensin II to chromatin underlies the aneuploidy in rbf1 mutants.
MeSH term(s)	Adenosine Triphosphatases/metabolism ; Animals ; Chromosome Structures/metabolism ; DNA-Binding Proteins/metabolism ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Humans ; Mitosis ; Models, Biological ; Multiprotein Complexes/metabolism ; Retinoblastoma Protein/genetics ; Retinoblastoma Protein/metabolism ; Transcription Factors/metabolism
Chemical Substances	DNA-Binding Proteins ; Drosophila Proteins ; Multiprotein Complexes ; Rbf protein, Drosophila ; Retinoblastoma Protein ; Transcription Factors ; condensin complexes ; Adenosine Triphosphatases (EC 3.6.1.-)
Language	English
Publishing date	2008-04-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	806684-x
ISSN	1549-5477 ; 0890-9369
ISSN (online)	1549-5477
ISSN	0890-9369
DOI	10.1101/gad.1666808
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Zs.A 2292: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 54: Show issues

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Article: Regulation of Bone Metabolism by Serotonin.

Lavoie, Brigitte / Lian, Jane B / Mawe, Gary M

Advances in experimental medicine and biology

2017 Volume 1033, Page(s) 35–46

Abstract: The processes of bone growth and turnover are tightly regulated by the actions of various signaling molecules, including hormones, growth factors, and cytokines. Imbalances in these processes can lead to skeletal disorders such as osteoporosis or high ... ...

Abstract	The processes of bone growth and turnover are tightly regulated by the actions of various signaling molecules, including hormones, growth factors, and cytokines. Imbalances in these processes can lead to skeletal disorders such as osteoporosis or high bone mass disease. It is becoming increasingly clear that serotonin can act through a number of mechanisms, and at different locations in the body, to influence the balance between bone formation and resorption. Its actions on bone metabolism can vary, based on its site of synthesis (central or peripheral) as well as the cells and subtypes of receptors that are activated. Within the central nervous system, serotonergic neurons act via the hypothalamus to suppress sympathetic input to the bone. Since sympathetic input inhibits bone formation, brain serotonin has a net positive effect on bone growth. Gut-derived serotonin is thought to inhibit bone growth by attenuating osteoblast proliferation via activation of receptors on pre-osteoblasts. There is also evidence that serotonin can be synthesized within the bone and act to modulate bone metabolism. Osteoblasts, osteoclasts, and osteocytes all have the machinery to synthesize serotonin, and they also express the serotonin-reuptake transporter (SERT). Understanding the roles of serotonin in the tightly balanced system of bone modeling and remodeling is a clinically relevant goal. This knowledge can clarify bone-related side effects of drugs that affect serotonin signaling, including serotonin-specific reuptake inhibitors (SSRIs) and receptor agonists and antagonists, and it can potentially lead to therapeutic approaches for alleviating bone pathologies.
MeSH term(s)	Animals ; Bone and Bones/metabolism ; Humans ; Osteogenesis/drug effects ; Osteogenesis/physiology ; Receptors, Serotonin/metabolism ; Serotonin/metabolism ; Serotonin Antagonists/pharmacology ; Serotonin Receptor Agonists/pharmacology ; Serotonin Uptake Inhibitors/pharmacology ; Signal Transduction/drug effects ; Signal Transduction/physiology
Chemical Substances	Receptors, Serotonin ; Serotonin Antagonists ; Serotonin Receptor Agonists ; Serotonin Uptake Inhibitors ; Serotonin (333DO1RDJY)
Language	English
Publishing date	2017-11-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-3-319-66653-2_3
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Article ; Online: Correction: Importin β2 mediates the spatio-temporal regulation of anillin through a noncanonical nuclear localization signal.

Chen, Anan / Akhshi, Tara K / Lavoie, Brigitte D / Wilde, Andrew

The Journal of biological chemistry

2018 Volume 293, Issue 47, Page(s) 18402

Language	English
Publishing date	2018-11-14
Publishing country	United States
Document type	Journal Article ; Published Erratum
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.AAC118.006473
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Article ; Online: Inhibition of polar actin assembly by astral microtubules is required for cytokinesis.

Chen, Anan / Ulloa Severino, Luisa / Panagiotou, Thomas C / Moraes, Trevor F / Yuen, Darren A / Lavoie, Brigitte D / Wilde, Andrew

Nature communications

2021 Volume 12, Issue 1, Page(s) 2409

Abstract: During cytokinesis, the actin cytoskeleton is partitioned into two spatially distinct actin isoform specific networks: a β-actin network that generates the equatorial contractile ring, and a γ-actin network that localizes to the cell cortex. Here we ... ...

Abstract	During cytokinesis, the actin cytoskeleton is partitioned into two spatially distinct actin isoform specific networks: a β-actin network that generates the equatorial contractile ring, and a γ-actin network that localizes to the cell cortex. Here we demonstrate that the opposing regulation of the β- and γ-actin networks is required for successful cytokinesis. While activation of the formin DIAPH3 at the cytokinetic furrow underlies β-actin filament production, we show that the γ-actin network is specifically depleted at the cell poles through the localized deactivation of the formin DIAPH1. During anaphase, CLIP170 is delivered by astral microtubules and displaces IQGAP1 from DIAPH1, leading to formin autoinhibition, a decrease in cortical stiffness and localized membrane blebbing. The contemporaneous production of a β-actin contractile ring at the cell equator and loss of γ-actin from the poles is required to generate a stable cytokinetic furrow and for the completion of cell division.
MeSH term(s)	Actin Cytoskeleton/metabolism ; Actins/metabolism ; Centrosome/metabolism ; Cytokinesis ; Formins/genetics ; Formins/metabolism ; HeLa Cells ; Humans ; Microscopy, Atomic Force ; Microscopy, Fluorescence ; Microtubule-Associated Proteins/genetics ; Microtubule-Associated Proteins/metabolism ; Microtubules/metabolism ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Protein Binding ; Spindle Apparatus/metabolism ; ras GTPase-Activating Proteins/genetics ; ras GTPase-Activating Proteins/metabolism ; rhoA GTP-Binding Protein/genetics ; rhoA GTP-Binding Protein/metabolism
Chemical Substances	Actins ; DIAPH1 protein, human ; DIAPH3 protein, human ; Formins ; IQ motif containing GTPase activating protein 1 ; Microtubule-Associated Proteins ; Neoplasm Proteins ; ras GTPase-Activating Proteins ; cytoplasmic linker protein 170 (148349-95-5) ; rhoA GTP-Binding Protein (EC 3.6.5.2)
Language	English
Publishing date	2021-04-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-22677-0
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