PUBLICATION
Regulatory significance of CULLIN2 in neuronal differentiation and regeneration
- Authors
- V, A.N., Satish, A., Balan, P., Korrapati, P.S.
- ID
- ZDB-PUB-220709-10
- Date
- 2022
- Source
- Neurochemistry international 159: 105386 (Journal)
- Registered Authors
- Keywords
- Cytokine signalling, Neural differentiation, Neural regeneration, Retinoic acid induction, Scaffold proteins, Zebra fish
- MeSH Terms
-
- Animals
- Cell Differentiation
- Nerve Regeneration/physiology
- Neurons
- Signal Transduction*
- Tretinoin/pharmacology
- Zebrafish*
- PubMed
- 35803325 Full text @ Neurochem. Int.
Citation
V, A.N., Satish, A., Balan, P., Korrapati, P.S. (2022) Regulatory significance of CULLIN2 in neuronal differentiation and regeneration. Neurochemistry international. 159:105386.
Abstract
Background Scaffold proteins coordinate multiple signalling pathways by integrating various proteins but the role of these proteins in neuronal pathways remains to be elucidated. The present study focused to evaluate the expression of the scaffold protein CULLIN2 in neuronal cells.
Methods The neuronal precursor cell line N2A was differentiated to neurons in-vitro with retinoic acid and biochemical assays were used to understand the gene expression profiling of CULLIN2. Moreover, neddylation inhibitor MLN4924 was used to inhibit the activity of CULLIN2 and the downstream substrates were validated. Finally, the role of CULLIN2 in nerve regeneration was evaluated in an in vivo zebrafish model.
Results Experimental data showed that the neuronal cells N2A have lower expression of CULLIN2 compared to skin cell lines (HaCaT and A431) and inactivation with the neddylation inhibitor resulted in cell death. Furthermore differentiating the neural precursor cell line into neurons with retinoic acid enhanced the expression of CULLIN2. Examining downstream signalling molecules with the neddylation inhibitor illuminates that MLN4924 treatment influences the cytokine signalling cascade (JAK-STAT) in neuronal cells. Moreover, for the first time, we show that the ubiquitin ligase protein CULLIN2 is perturbed in neural regeneration. Expression profile of CULLIN2 was significantly decreased in response to a nerve injury in Zebra fish and as the nerve regenerates there is corresponding reduction in the mRNA levels.
Conclusion During differentiation CULLIN2 is upregulated whereas during regeneration there is significant downregulation. Thus, our findings reveal a crucial role of the scaffold protein CULLIN2 in nerve differentiation and regeneration which can be vital for the treatment of nerve injury.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping