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ORIGINAL RESEARCH article

Front. Mol. Neurosci.
Sec. Molecular Signalling and Pathways
Volume 17 - 2024 | doi: 10.3389/fnmol.2024.1494160

Perinuclear compartment controls calcineurin/MEF2 signaling for axonal outgrowth of hippocampal neurons

Provisionally accepted
Joanna Mackiewicz Joanna Mackiewicz 1Malwina Lisek Malwina Lisek 1Agata Sakowicz Agata Sakowicz 2Feng Guo Feng Guo 3,4*Tomasz Boczek Tomasz Boczek 1*
  • 1 Department of Molecular Neurochemistry, Medical University of Lodz, Lodz, Poland
  • 2 Department of Medical Biotechnology, Medical University of Lodz, Łódź, Łódź, Poland
  • 3 Department of Pharmaceutical Toxicology ,China Medical University, Shenyang, China, Shenyang, China
  • 4 Department of Pharmacy, Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China

The final, formatted version of the article will be published soon.

    Central to the process of axon elongation is the concept of compartmentalized signaling, which involves the A-kinase anchoring protein (AKAP)-dependent organization of signaling pathways within distinct subcellular domains. This spatial organization is also critical for translating electrical activity into biochemical events. Despite intensive research, the detailed mechanisms by which the spatial separation of signaling pathways governs axonal outgrowth and pathfinding remain unresolved. In this study, we demonstrate that mAKAPα (AKAP6), located in the perinuclear space of primary hippocampal neurons, scaffolds calcineurin, NFAT, and MEF2 transcription factors for activitydependent axon elongation. By employing anchoring disruptors, we show that the mAKAPα/calcineurin/MEF2 signaling pathway, but not NFAT, drives the process of axonal outgrowth. Furthermore, mAKAPα-controlled axonal elongation is linked to the changes in the expression of genes involved in Ca 2+ /cAMP signaling. These findings reveal a novel regulatory mechanism of axon growth that could be targeted therapeutically for neuroprotection and regeneration.

    Keywords: mAKAP signalosome, hippocampal neurons, Calcineurin, MEF2, axonal outgrowth, neuronal development, perinuclear space

    Received: 10 Sep 2024; Accepted: 04 Nov 2024.

    Copyright: © 2024 Mackiewicz, Lisek, Sakowicz, Guo and Boczek. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Feng Guo, Department of Pharmaceutical Toxicology ,China Medical University, Shenyang, China, Shenyang, China
    Tomasz Boczek, Department of Molecular Neurochemistry, Medical University of Lodz, Lodz, 92-215, Poland

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.