Related Experiment Video

Updated: Jun 6, 2025

Methods for the Modulation and Analysis of NF-κB-dependent Adult Neurogenesis
14:58

Methods for the Modulation and Analysis of NF-κB-dependent Adult Neurogenesis

Published on: February 13, 2014

14.3K

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
PubMed

Insights

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.
Keywords:
AKAP6BDNFCalcineurinNFATc4Neuroprotection

More Related Videos

An Improved Protocol to Purify and Directly Mono-Biotinylate Recombinant BDNF in a Tube for Cellular Trafficking Studies in Neurons13:46

An Improved Protocol to Purify and Directly Mono-Biotinylate Recombinant BDNF in a Tube for Cellular Trafficking Studies in Neurons

Published on: July 11, 2020

5.7K
Cellular Membrane Affinity Chromatography Columns to Identify Specialized Plant Metabolites Interacting with Immobilized Tropomyosin Kinase Receptor B11:44

Cellular Membrane Affinity Chromatography Columns to Identify Specialized Plant Metabolites Interacting with Immobilized Tropomyosin Kinase Receptor B

Published on: January 19, 2022

2.5K

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-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...
7.2K
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
77.3K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.4K
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...
2.4K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/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...
3.4K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.3K