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Genetic Manipulation of Cerebellar Granule Neurons In Vitro and In Vivo to Study Neuronal Morphology and Migration
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BARS Influences Neuronal Development by Regulation of Post-Golgi Trafficking
Laura Gastaldi1,2, Josefina Inés Martín1, Lucas Javier Sosa3
1Instituto de Investigación Médica Mercedes y Martín Ferreyra (INIMEC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Córdoba, Córdoba 5016, Argentina.
Cells
|April 23, 2022
Summary
Brefeldin A-Ribosylated Substrate (BARS) regulates neuronal development by controlling membrane protein exit from the Golgi apparatus. Suppressing BARS inhibits neuron growth and migration, impacting axonal and dendritic formation.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Neurons require precise membrane protein trafficking for specialized compartments like axons and dendrites.
- Disruption of the Golgi apparatus (GA) secretory pathway impairs neuronal development and polarity.
Purpose of the Study:
- To investigate the role of Brefeldin A-Ribosylated Substrate (CtBP1-S/BARS) in neuronal morphological polarization.
- To determine BARS's function in the exit of membrane proteins from the Trans Golgi Network (TGN).
Main Methods:
- Analyzed BARS expression during in vitro neuronal development.
- Utilized RNA interference (RNAi) to suppress BARS in hippocampal neurons and during in situ cortical development.
- Employed GFP-tagged plasma membrane proteins with reversible aggregation domains to track protein exit from the GA.
Main Results:
- BARS is expressed in developing neurons.
- RNAi suppression of BARS inhibited axonal and dendritic elongation in vitro.
- BARS suppression perturbed neuronal migration and multipolar-to-bipolar transition in vivo.
- Dominant-negative BARS expression delayed the exit of membrane protein carriers from the GA.
Conclusions:
- BARS plays a crucial role in neuronal development.
- BARS regulates post-Golgi membrane trafficking, impacting neuronal polarity and morphology.
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