Related Experiment Video

Updated: Aug 2, 2025

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

8.7K

Characterization of serotonin-5-HTR1E signaling pathways and its role in cell survival

Vinay Kumar Sharma1, Kiersten Campbell2, Xuyu Yang1

  • 1Section on Cellular Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|April 20, 2023
PubMed

Insights

Serotonin binding to 5-Hydroxytryptamine receptor 1E (5-HTR1E) activates cyclic AMP (cAMP) and extracellular-signal related kinases (ERK) pathways, crucial for cell survival. This receptor

Area of Science:

  • Cellular and Molecular Biology
  • Neuropharmacology
  • Signal Transduction

Background:

  • The precise signaling mechanisms of 5-Hydroxytryptamine receptor 1E (5-HTR1E) activation by serotonin remain incompletely understood.
  • While 5-HTR1E is known to influence cyclic AMP (cAMP) and extracellular-signal related kinases (ERK) pathways, the specific cellular regulators involved are not fully elucidated.

Purpose of the Study:

  • To investigate the detailed cellular mechanisms of serotonin-induced 5-HTR1E signaling pathways, focusing on cAMP and ERK activation.
  • To determine the role of 5-HTR1E in cell cycle regulation and cell survival.
  • To identify novel gene expression changes regulated by 5-HTR1E.

Main Methods:

  • Utilized HEK293 cells overexpressing 5-HTR1E for signaling pathway analysis.
  • Employed Pertussis Toxin (PTX) and protein kinase A (PKA) inhibitors to dissect signaling cascades.
  • Conducted siRNA-mediated gene knockdown in SH-SY5Y cells and MTT assays for cell survival analysis.
  • Performed RNA-sequencing (RNA-seq) to identify regulated genes in 5-HTR1E overexpressing cells.

Main Results:

  • Serotonin-induced 5-HTR1E activation of cAMP and ERK pathways is mediated by a Gαi-linked cascade, independent of Gβγ, Gq, and β-arrestin.
  • PKA inhibition affected ERK signaling but not cAMP, suggesting distinct regulatory roles.
  • 5-HTR1E knockdown in neuronal and cancer cell lines significantly reduced cell survival and expression of cell cycle/survival genes (c-Myc, Cyclin D1, Cyclin E, BCL2).
  • RNA-seq revealed 5-HTR1E regulates expression of RAMP1, NR4A1, and other cyclin genes.

Conclusions:

  • Serotonin binding to 5-HTR1E simultaneously activates cAMP and ERK signaling pathways in HEK293 cells via a Gαi-dependent mechanism.
  • 5-HTR1E plays a critical role in regulating cell cycle progression and promoting cell survival.
  • The findings provide novel insights into the signaling and functional significance of 5-HTR1E in cellular processes.
Keywords:
G proteinsGPCRcell signalingcell survival

More Related Videos

Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model08:15

Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model

Published on: June 6, 2025

117
Real-Time Impedance-based Cell Analyzer as a Tool to Delineate Molecular Pathways Involved in Neurotoxicity and Neuroprotection in a Neuronal Cell Line08:23

Real-Time Impedance-based Cell Analyzer as a Tool to Delineate Molecular Pathways Involved in Neurotoxicity and Neuroprotection in a Neuronal Cell Line

Published on: August 9, 2014

11.5K

Related Concept Videos

Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
Diversity in Cell Signaling Responses01:22

Diversity in Cell Signaling Responses

The physiological function of a cell and cellular communication are outcomes of a range of extrinsic signals, intracellular signaling pathways, and cellular responses. No two cell types express the same repertoire of signaling components. Receptors are highly selective for their cognate ligands, but once activated, they can alter multiple cellular processes such as DNA transcription, protein synthesis, and metabolic activity. 
Graded and Abrupt Responses
Some signaling systems generate...
6.5K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.5K
Sympathetic Signaling01:31

Sympathetic Signaling

Sympathetic signaling, a vital part of the autonomic nervous system, plays a crucial role in mobilizing the body's resources in response to stress or emergencies. It involves the transmission of nerve impulses from sympathetic preganglionic fibers to postganglionic fibers. This results in the release of specific neurotransmitters and activation of adrenergic receptors.
Sympathetic preganglionic fibers release the neurotransmitter acetylcholine (ACh) onto the ganglionic neurons in the...
1.1K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.5K