Caldendrin–Jacob: A Protein Liaison That Couples NMDA Receptor Signalling to the Nucleus
Author Information
Author(s): Dieterich Daniela C, Karpova Anna, Mikhaylova Marina, Zdobnova Irina, König Imbritt, Landwehr Marco, Kreutz Martin, Smalla Karl-Heinz, Richter Karin, Landgraf Peter, Reissner Carsten, Boeckers Tobias M, Zuschratter Werner, Spilker Christina, Seidenbecher Constanze I, Garner Craig C, Gundelfinger Eckart D, Kreutz Michael R
Primary Institution: Leibniz-Institute for Neurobiology, Magdeburg, Germany
Hypothesis
Caldendrin might have specific functions in neurons that are distinct from those of calmodulin.
Conclusion
The study identifies a novel mechanism of synapse-to-nucleus communication that links NMDA receptor activity to nuclear signaling events involved in neuronal degeneration and synaptic plasticity.
Supporting Evidence
- Jacob is recruited to neuronal nuclei upon NMDA receptor activation.
- Nuclear knockdown of Jacob prevents CREB shut-off after extrasynaptic NMDA receptor activation.
- Nuclear overexpression of Jacob induces CREB shut-off without NMDA receptor stimulation.
- Jacob's nuclear accumulation results in a rapid stripping of synaptic contacts.
- Caldendrin binds to Jacob's nuclear localization signal in a Ca2+-dependent manner.
- Jacob is highly enriched in euchromatin fractions associated with gene transcription.
- Activation of extrasynaptic NMDA receptors is crucial for Jacob's nuclear import.
- Knockdown of nuclear Jacob prevents NMDA-induced loss of synaptic contacts.
Takeaway
This study shows that a protein called Jacob helps send signals from the NMDA receptors in brain cells to the nucleus, which can affect how the cells grow and survive.
Methodology
The study utilized yeast two-hybrid screening, immunostaining, and various biochemical assays to investigate the interactions and functions of Caldendrin and Jacob.
Limitations
The study primarily focuses on in vitro experiments, which may not fully replicate in vivo conditions.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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