The Jak/STAT pathway is involved in synaptic plasticity
Céline S Nicolas1, Stéphane Peineau, Mascia Amici
1MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, Medical Sciences Building, University Walk, Bristol BS8 1TD, UK.
Abstract:
The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is involved in many cellular processes, including cell growth and differentiation, immune functions and cancer. It is activated by various cytokines, growth factors, and protein tyrosine kinases (PTKs) and regulates the transcription of many genes. Of the four JAK isoforms and seven STAT isoforms known, JAK2 and STAT3 are highly expressed in the brain where they are present in the postsynaptic density (PSD). Here, we demonstrate a new neuronal function for the JAK/STAT pathway. Using a variety of complementary approaches, we show that the JAK/STAT pathway plays an essential role in the induction of NMDA-receptor dependent long-term depression (NMDAR-LTD) in the hippocampus. Therefore, in addition to established roles in cytokine signaling, the JAK/STAT pathway is involved in synaptic plasticity in the brain.
Insights
The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is crucial for brain synaptic plasticity. This pathway regulates NMDA-receptor dependent long-term depression in the hippocampus.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Signaling
Background:
- The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway regulates critical cellular processes like cell growth, differentiation, immune functions, and cancer.
- JAK2 and STAT3 are highly expressed in the brain, particularly in the postsynaptic density (PSD).
Purpose of the Study:
- To investigate a novel neuronal function of the JAK/STAT pathway.
- To determine the role of the JAK/STAT pathway in synaptic plasticity, specifically in NMDA-receptor dependent long-term depression (NMDAR-LTD) in the hippocampus.
Main Methods:
- Utilized a variety of complementary experimental approaches.
- Focused on the hippocampus to study NMDAR-LTD induction.
Main Results:
- Demonstrated that the JAK/STAT pathway plays an essential role in the induction of NMDAR-LTD.
- Confirmed the presence and function of JAK2 and STAT3 in the PSD.
Conclusions:
- The JAK/STAT pathway has a significant role in synaptic plasticity within the brain.
- Beyond its established roles in cytokine signaling, the JAK/STAT pathway is implicated in neuronal function and learning/memory processes.
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