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Updated: Jun 4, 2025
Transpupillary Two-Photon In Vivo Imaging of the Mouse Retina
Published on: February 13, 2021
Marcks overexpression in retinal ganglion cells promotes optic nerve regeneration
Xue-Qi Peng1,2,3,4, Yan-Zhong Li1,2,3,4, Chen Gu1,2,3,4
1Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Abstract:
Regeneration of injured central nervous system (CNS) axons is highly restricted, leading to permanent neurological deficits. The myristoylated alanine-rich C-kinase substrate (MARCKS) is a membrane-associated protein kinase C (PKC) substrate ubiquitously expressed in eukaryotic cells, plays critical roles in development, brain plasticity, and tissues regeneration. However, little is known about the role of Marcks in CNS axon regeneration. Here we show that Marcks overexpression promotes robust axon regeneration either before or after optic nerve crush, but insignificantly impacts neuronal survival. Notably, immunostaining and RNA sequencing demonstrate that Marcks overexpression does not affect known regeneration-associated genes and pathways. Furthermore, combining CNTF which activates the JAK-STAT3 pathway and Marcks overexpression further enhances axon regeneration. Finally, we demonstrate functionally essential effector domain (ED) of MARCKS has similar effects on inducing axon regeneration in RGCs. These results suggest that manipulating Marcks and its ED may become a therapeutic approach to promote axon regeneration after CNS injury.
Insights
Overexpressing the myristoylated alanine-rich C-kinase substrate (MARCKS) protein promotes central nervous system axon regeneration after injury. Manipulating MARCKS or its effector domain may offer new therapeutic strategies for CNS repair.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Molecular Biology
Background:
- Central nervous system (CNS) axon regeneration is limited, causing permanent deficits.
- Myristoylated alanine-rich C-kinase substrate (MARCKS) is involved in cell plasticity and regeneration.
- The role of MARCKS in CNS axon regeneration remains largely unknown.
Purpose of the Study:
- To investigate the role of MARCKS in promoting CNS axon regeneration.
- To explore potential therapeutic applications of MARCKS for CNS injury.
Main Methods:
- Overexpression of Marcks in neurons.
- Optic nerve crush model.
- Immunostaining and RNA sequencing.
- Functional assessment of MARCKS effector domain (ED).
Main Results:
- Marcks overexpression significantly enhanced axon regeneration after optic nerve injury.
- Neuronal survival was not significantly affected by Marcks overexpression.
- Marcks overexpression did not alter known regeneration-associated genes or pathways.
- Combined CNTF and Marcks overexpression further boosted regeneration.
- The effector domain (ED) of MARCKS alone promoted axon regeneration in retinal ganglion cells (RGCs).
Conclusions:
- MARCKS plays a crucial role in promoting CNS axon regeneration.
- MARCKS manipulation, particularly its effector domain, presents a potential therapeutic avenue for CNS injuries.
- This study opens new possibilities for enhancing recovery from neurological damage.
