VPS35 regulates developing mouse hippocampal neuronal morphogenesis by promoting retrograde trafficking of BACE1
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Updated: May 15, 2026
Ex Utero Electroporation and Organotypic Slice Culture of Mouse Hippocampal Tissue
Published on: March 4, 2015
Chun-Lei Wang1, Fu-Lei Tang, Yun Peng
1Institute of Molecular Medicine and Genetics, and Department of Neurology, Medical College of Georgia, Georgia Health Sciences University , Augusta, GA 30912 , USA.
Abstract:
VPS35, a major component of the retromer, plays an important role in the selective endosome-to-Golgi retrieval of membrane proteins. Dysfunction of retromer is a risk factor for neurodegenerative disorders, but its function in developing mouse brain remains poorly understood. Here we provide evidence for VPS35 promoting dendritic growth and maturation, and axonal protein transport in developing mouse hippocampal neurons. Embryonic hippocampal CA1 neurons suppressing Vps35 expression by in utero electroporation of its micro RNAs displayed shortened apical dendrites, reduced dendritic spines, and swollen commissural axons in the neonatal stage, those deficits reflecting a defective protein transport/trafficking in developing mouse neurons. Further mechanistic studies showed that Vps35 depletion in neurons resulted in an impaired retrograde trafficking of BACE1 (β1-secretase) and altered BACE1 distribution. Suppression of BACE1 expression in CA1 neurons partially rescued both dendritic and axonal deficits induced by Vps35-deficiency. These results thus demonstrate that BACE1 acts as a critical cargo of retromer in vitro and in vivo, and suggest that VPS35 plays an essential role in regulating apical dendritic maturation and in preventing axonal spheroid formation in developing hippocampal neurons.
Insights
VPS35 protein is crucial for neuron development, promoting dendritic growth and axonal transport. Its deficiency impairs protein trafficking, affecting neuron structure and function in developing mouse brains.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- The retromer complex, including VPS35, is vital for endosome-to-Golgi retrieval.
- Retromer dysfunction is linked to neurodegenerative diseases.
- VPS35 function in the developing mouse brain is not well understood.
Purpose of the Study:
- To investigate the role of VPS35 in the development of mouse hippocampal neurons.
- To elucidate the mechanisms by which VPS35 influences neuronal structure and protein transport.
Main Methods:
- In utero electroporation of microRNAs to suppress Vps35 expression in embryonic hippocampal CA1 neurons.
- Analysis of dendritic morphology, spine density, and axonal structure.
- Investigation of BACE1 trafficking and distribution in Vps35-depleted neurons.
- Assessment of the impact of BACE1 suppression on neuronal deficits.
Main Results:
- VPS35 suppression led to shortened apical dendrites, reduced dendritic spines, and axonal swelling.
- Vps35 depletion impaired retrograde trafficking of BACE1 (β1-secretase) and altered its distribution.
- Reducing BACE1 levels partially rescued the dendritic and axonal defects caused by Vps35 deficiency.
Conclusions:
- VPS35 promotes dendritic maturation and axonal protein transport in developing hippocampal neurons.
- BACE1 is identified as a critical cargo of the retromer complex, both in vitro and in vivo.
- VPS35 plays an essential role in regulating neuronal development and preventing axonal abnormalities.
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