CREB3L2 Modulates Nerve Growth Factor-Induced Cell Differentiation
Luciana Sampieri1,2, Macarena Funes Chabán1,2, Pablo Di Giusto1,2
1Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Córdoba, Argentina.
Frontiers in Molecular Neuroscience
|August 23, 2021
Summary
Nerve growth factor (NGF) triggers neuronal differentiation by altering the Golgi and increasing CREB3L2 expression. This transcription factor regulates neurite outgrowth and Rab5 GTPase activity during cell differentiation.
Area of Science:
- Cell Biology
- Neuroscience
- Molecular Biology
Background:
- Nerve growth factor (NGF) is crucial for neuronal growth, differentiation, and survival.
- NGF-induced processes necessitate secretory pathway adaptation, involving membrane remodeling.
- CREB3 transcription factors regulate secretory pathways and Golgi homeostasis, but their role in cell differentiation is unclear.
Purpose of the Study:
- To investigate the expression and signaling of CREB3 transcription factors during NGF-induced PC12 cell differentiation.
- To elucidate the role of CREB3L2 in neuronal differentiation.
Main Methods:
- Utilized the NGF-induced PC12 cell differentiation model.
- Analyzed protein and mRNA expression of CREB3 family members.
- Investigated the involvement of MAPK and cAMP signaling pathways.
- Assessed the impact of CREB3L2 manipulation on neurite outgrowth and Rab5 GTPase levels.
Main Results:
- NGF treatment induced Golgi enlargement and increased expression of membrane transport proteins.
- CREB3L2 protein and mRNA levels significantly increased upon NGF stimulation, requiring MAPK and cAMP pathways.
- CREB3L2 overexpression inhibited NGF-induced neurite outgrowth, while its depletion enhanced differentiation.
- CREB3L2 levels inversely correlated with Rab5 GTPase immunofluorescence intensity.
Conclusions:
- CREB3L2 is a key downstream target of NGF signaling pathways involved in neuronal differentiation.
- CREB3L2 acts as a regulator of neurite outgrowth and Rab5 GTPase activity during NGF-mediated differentiation.
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