Related Experiment Video
Updated: May 16, 2026
07:28
An Inexpensive, Scalable Behavioral Assay for Measuring Ethanol Sedation Sensitivity and Rapid Tolerance in Drosophila
Published on: April 15, 2015
JNK pathway activation is controlled by Tao/TAOK3 to modulate ethanol sensitivity
David Kapfhamer1, Ian King, Mimi E Zou
1The Ernest Gallo Clinic and Research Center, University of California San Francisco, Emeryville, California, United States of America.
Plos One
|December 11, 2012
Summary
The Sterile20 kinase TAO/TAOK3 regulates ethanol
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- JNK MAP kinase pathway signaling is modulated by ethanol but its behavioral relevance and regulation remain unclear.
- Understanding the upstream regulators of JNK signaling is crucial for deciphering neuronal responses to ethanol.
Purpose of the Study:
- To investigate the role of the TAO/TAOK3 kinase in regulating JNK signaling and behavioral responses to acute ethanol exposure.
- To determine if the identified pathway is conserved across species, specifically in Drosophila and mice.
Main Methods:
- Utilized Drosophila melanogaster and Mus musculus models.
- Employed genetic manipulation of tao/Taok3 and JNK pathway genes.
- Assessed behavioral sensitivity to ethanol and measured JNK pathway activity (phospho-JNK levels).
Main Results:
- TAO/TAOK3 functions upstream of JNK signaling to control ethanol-induced behavioral effects in both flies and mice.
- Disruption of TAO/TAOK3 or JNK pathway genes altered sensitivity to ethanol's stimulant and sedative effects.
- TAO/TAOK3 deficiency conferred resistance to ethanol's sedative effects in mice, with occluded JNK activation by ethanol.
Conclusions:
- A conserved TAO/TAOK3-JNK neuronal signaling pathway regulates sensitivity to acute ethanol exposure.
- This pathway represents a potential target for understanding and modulating ethanol's effects.
Related Concept Videos
01:07MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
01:19Interactions 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...
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...
02:26NF-κB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
01:22PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...
02:26NF-kB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...