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AKAP6 controls NFATc4 activity for BDNF-mediated neuroprotection
Joanna Mackiewicz1, Julia Tomczak1, Malwina Lisek1
1Department of Molecular Neurochemistry, Medical University of Lodz, Lodz, Poland.
Molecular Brain
|November 23, 2024
Summary
A-kinase anchoring protein 6 (AKAP6) is crucial for brain-derived neurotrophic factor (BDNF)-mediated neuronal survival. AKAP6 anchors calcineurin and NFATc4, essential for BDNF
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Brain-derived neurotrophic factor (BDNF) exhibits significant prosurvival effects in neuronal models.
- A-kinase anchoring proteins (AKAPs) are implicated in orchestrating BDNF signaling pathways.
- AKAP6 is specifically involved in neurotrophin-mediated survival of retinal ganglion cells (RGCs).
Purpose of the Study:
- To elucidate the molecular mechanisms by which AKAP6 mediates BDNF-dependent neuronal survival.
- To investigate the role of AKAP6 in regulating BDNF-induced NFAT transcriptional activity.
- To determine the downstream targets of BDNF neuroprotection involving AKAP6.
Main Methods:
- Investigated AKAP6's role in anchoring calcineurin (CaN) and nuclear factor of activated T cells (NFATc4).
- Assessed the impact of disrupting CaN anchoring on BDNF's pro-survival effects.
- Utilized NFATc4 knockout (NFATc4-/-) mice to study in vivo neuroprotection.
Main Results:
- AKAP6 anchors CaN and NFATc4, regulating BDNF-mediated NFAT transcriptional activity essential for neuronal survival.
- Disruption of CaN anchoring by AKAP6 significantly reduces BDNF's pro-survival effects.
- NFATc4 acts as a downstream mediator of BDNF-induced neuroprotection in vivo.
Conclusions:
- AKAP6 is a critical regulator of BDNF-mediated neuronal survival by anchoring key signaling molecules.
- The AKAP6-CaN-NFATc4 complex is vital for BDNF's neuroprotective actions.
- Targeting this pathway may offer novel therapeutic strategies for neurodegenerative diseases and neuronal injury.
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