Gi-Coupled Receptor Activation Potentiates Piezo2 Currents via Gβγ

Rosario, Del; Yudin, Yevgen; Su, Songxue; Hartle, Cassandra M.; Mirshahi, Tooraj; Rohács, Tibor

doi:10.1101/722637

Cited by 4 publications

(5 citation statements)

References 60 publications

(74 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We considered currents to be rapidly adapting, if they fully inactivated before end of the 200 ms mechanical stimulus. The inactivation time constants (tau) of these currents were 17.95 ± 2.4 ms, similar to that in our earlier work (Borbiro et al, 2015; Del Rosario et al, 2020). Intermediate adapting currents did not fully inactivate, but the leftover current at the end of the mechanical simulation was less that 50% of the peak current.…”

Section: Methodssupporting

confidence: 90%

See 1 more Smart Citation

TMEM120A/TACAN inhibits mechanically activated Piezo2 channels

Rosario

Gabrielle

Yudin

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Mechanically activated Piezo2 channels are key mediators of light touch and proprioception in mice and humans. Relatively little is known about what other proteins regulate Piezo2 activity in a cellular context. TACAN (TMEM120A) was proposed to act as a high threshold mechanically activated ion channel in nociceptive dorsal root ganglion (DRG) neurons. Here we find that TACAN co-expression robustly reduced mechanically activated Piezo2 currents, but did not inhibit mechanically activated Piezo1 and TREK1 currents. TACAN co-expression did not affect cell surface expression of either Piezo1 or Piezo2 and did not have major effects on the cortical actin or tubulin cytoskeleton. TACAN expression alone did not result in the appearance of mechanically activated currents above background. In addition, TACAN and Piezo2 expression in DRG neurons overlapped, and siRNA mediated knockdown of TACAN did not decrease the proportion of slowly adapting mechanically activated currents, but resulted in an increased proportion of rapidly adapting currents. Our data do not support TACAN being a mechanically activated ion channel, and identify it as a negative modulator of Piezo2 channel activity.

show abstract

Section: Methodssupporting

confidence: 90%

“…DRG neurons were isolated as described previously (Borbiro et al, 2015; Del Rosario et al, 2020). All animal procedures were approved by the Institutional Animal Care and Use Committee at Rutgers NJMS.…”

Section: Methodsmentioning

confidence: 99%

TMEM120A/TACAN inhibits mechanically activated Piezo2 channels

Rosario

Gabrielle

Yudin

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Co-activation of both 5-HT1A and 5-HT2A in cortical pyramidal neurons leads to complex physiologic responses [ 65 , 66 ] that are further regulated by 5HT1A receptors on local inhibitory neurons [ 67 ]. The effects of receptor activation can also vary depending on inputs from other neuromodulators [ 68 ] and the differential activation of downstream effectors [ 65 , 69 ].These studies highlight the difficulties of predicting the effects of serotonin receptor activation based solely on expression data, and the need for physiological assays to assess their role in specific circuits. Although two recent studies have reported serotonin receptor expression in visual neurons [ 70 , 71 ], to our knowledge there is no information on the physiological effect(s) of any serotonin receptor in any of the interneurons within the insect visual system.…”

Section: Introductionmentioning

confidence: 99%

Serotonergic modulation of visual neurons in Drosophila melanogaster

et al. 2020

View full text Add to dashboard Cite

Sensory systems rely on neuromodulators, such as serotonin, to provide flexibility for information processing as stimuli vary, such as light intensity throughout the day. Serotonergic neurons broadly innervate the optic ganglia of Drosophila melanogaster, a widely used model for studying vision. It remains unclear whether serotonin modulates the physiology of interneurons in the optic ganglia. To address this question, we first mapped the expression patterns of serotonin receptors in the visual system, focusing on a subset of cells with processes in the first optic ganglion, the lamina. Serotonin receptor expression was found in several types of columnar cells in the lamina including 5-HT2B in lamina monopolar cell L2, required for spatiotemporal luminance contrast, and both 5-HT1A and 5-HT1B in T1 cells, whose function is unknown. Subcellular mapping with GFP-tagged 5-HT2B and 5-HT1A constructs indicated that these receptors localize to layer M2 of the medulla, proximal to serotonergic boutons, suggesting that the medulla neuropil is the primary site of serotonergic regulation for these neurons. Exogenous serotonin increased basal intracellular calcium in L2 terminals in layer M2 and modestly decreased the duration of visually induced calcium transients in L2 neurons following repeated dark flashes, but otherwise did not alter the calcium transients. Flies without functional 5-HT2B failed to show an increase in basal calcium in response to serotonin. 5-HT2B mutants also failed to show a change in amplitude in their response to repeated light flashes but other calcium transient parameters were relatively unaffected. While we did not detect serotonin receptor expression in L1 neurons, they, like L2, underwent serotonin-induced changes in basal calcium, presumably via interactions with other cells. These data demonstrate that serotonin modulates the physiology of interneurons involved in early visual processing in Drosophila.

show abstract

“…Several studies have demonstrated that MAPK pathways can modulate Piezo2 currents (Doihara et al, 2009b). In addition, literature suggests that AS-IV has antiinflammatory properties by inhibiting the phosphorylation of ERK1/2 and p38 in various diseases, such as atherosclerosis and hepatic steatosis (Gao et al, 2017;Del Rosario et al, 2020;Chen et al, 2021). Therefore, we investigated the activation of MAPK pathways in mouse colon and observed a significant increase in p-p38 and p-ERK levels in STC tissue, while their expression decreased in the Lop + AS group.…”

Section: Discussionmentioning

confidence: 89%

Astragaloside IV improves slow transit constipation by regulating gut microbiota and enterochromaffin cells

Wan,

Zhou,

Chen

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

Purpose: Slow transit constipation (STC) is a common gastrointestinal disorder characterized by altered gut microbiota and reduced number of enterochromaffin cells (ECs). Astragaloside IV (AS-IV), a low drug permeability saponin, has showed beneficial effects on patients with STC. However, the specific mechanism by which AS-IV regulates STC remains unclear. In this study, we aimed to investigate the effect of AS-IV on STC and its associated mechanisms involving gut microbiota.Methods: The effect of AS-IV on STC was evaluated on STC mice induced with loperamide. We measured defecation frequency, intestinal mobility, ECs loss, and colonic lesions in STC mice treated with AS-IV. We also analyzed the changes in gut microbiota and metabolites after AS-IV treatment. Moreover, we investigated the relationship between specific gut microbes and altered fecal metabolites, such as 3-bromotyrosine (3-BrY). We also conducted in vitro experiments to investigate the effect of 3-BrY on caspase-dependent apoptosis of ECs and the activation of the p38 MAPK and ERK signaling pathways induced by loperamide.Results: AS-IV treatment promoted defecation, improved intestinal mobility, suppressed ECs loss, and alleviated colonic lesions in STC mice. AS-IV treatment also affected gut microbiota and metabolites, with a significant correlation between specific gut microbes and altered fecal metabolites such as 3-BrY. Furthermore, 3-BrY may potentially reduce caspase-dependent apoptosis of ECs and protect cell survival by inhibiting the activation of the p38 MAPK and ERK signaling pathways induced by loperamide.Conclusion: Our findings suggest that changes in gut microbiota and ECs mediated the therapeutic effect of STC by AS-IV. These results provide a basis for the use of AS-IV as a prebiotic agent for treating STC. The specific mechanism by which AS-IV regulates gut microbiota and ECs warrants further investigation.

show abstract

Gi-Coupled Receptor Activation Potentiates Piezo2 Currents via Gβγ

Cited by 4 publications

References 60 publications

TMEM120A/TACAN inhibits mechanically activated Piezo2 channels

TMEM120A/TACAN inhibits mechanically activated Piezo2 channels

Serotonergic modulation of visual neurons in Drosophila melanogaster

Astragaloside IV improves slow transit constipation by regulating gut microbiota and enterochromaffin cells

Contact Info

Product

Resources

About