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The Chromatin-Modifying Protein RCOR2/CoREST2 Safeguards Axon-Dendrite Growth and Microtubule Stability in Brain
Carlos Wilson1,2, Victoria Rozés-Salvador2,3, José F Drube1
1Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC) I Centro de Investigación en Medicina Traslacional "Severo R. Amuchástegui" (CIMETSA) U.A. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET); Av. Naciones Unidas 420, Barrio Parque Vélez Sarsfield, X5016KEJ -, Córdoba, Argentina.
Journal of Neurochemistry
|May 19, 2026
Summary
The chromatin modifier RCOR2 (CoREST2) is vital for maintaining neuronal structure in developing neurons. Its knockdown impairs axon and dendrite growth by affecting microtubule stability, highlighting its neuroprotective role.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Neuronal dynamics are key to brain health.
- RCOR2 (CoREST2) is a chromatin modifier with known neuroprotective roles in neurogenesis and aging.
- RCOR2's function in post-mitotic neurons is understudied.
Purpose of the Study:
- To investigate the role of RCOR2 in the structural integrity of post-mitotic neurons.
- To elucidate the molecular mechanisms underlying RCOR2's neuroprotective functions.
Main Methods:
- Primary culture of embryonic rat hippocampal neurons.
- Confocal, AiryScan2, and STED microscopy.
- shRNA-mediated knockdown of RCOR2.
- qRT-PCR, immunoblotting, and z-stack imaging.
- Treatment with taxol.
Main Results:
- RCOR2 is localized in neuronal nuclei, maintaining heterochromatin organization.
- RCOR2 knockdown led to shortened axons and dendrites.
- Knockdown neurons exhibited abnormal accumulation of microtubule-associated proteins (MAPs) like MAP2 and Tau.
- RCOR2 knockdown reduced microtubule stability, indicated by an increased tyrosinated-tubulin/acetylated-tubulin ratio.
- Taxol treatment partially rescued neuritic growth in RCOR2 knockdown neurons.
Conclusions:
- RCOR2 plays a crucial role in preserving the structural integrity of axons and dendrites in developing neurons.
- RCOR2's function is mediated through the regulation of microtubule stability.
- These findings reveal neuron-specific functions of RCOR2, emphasizing its importance in neuronal architecture and brain health.
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