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Sunday Driver Mediates Multi-Compartment Golgi Outposts Defects Induced by Amyloid Precursor Protein
Qianqian Du1,2, Jin Chang1,2, Guo Cheng1,2
1Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan, China.
Frontiers in Neuroscience
|June 18, 2021
Summary
Alzheimer's disease (AD) involves Golgi defects. Amyloid precursor protein (APP) disrupts Golgi outpost (GO) movement in dendrites via dynein heavy chain (Dhc) and Sunday driver (Syd), offering new insights into AD.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Golgi fragmentation is a hallmark of Alzheimer's disease (AD).
- Amyloid precursor protein (APP) causes Golgi fragmentation in the cell body.
- The role of APP in regulating Golgi outposts (GOs) within neuronal dendrites is not well understood.
Purpose of the Study:
- To investigate how APP influences the movement of Golgi outposts (GOs) in dendrites.
- To elucidate the molecular mechanisms underlying APP's regulation of GO dynamics in the context of AD.
Main Methods:
- Utilized knockdown experiments in *Drosophila* larvae to assess the roles of motor proteins.
- Conducted loss-of-function screening to identify key regulatory proteins.
- Analyzed the distribution and movement of multi-compartment GOs (mcGOs) in response to APP modulation.
Main Results:
- Bidirectional movement of mcGOs is regulated by both dynein heavy chain (Dhc) and kinesin heavy chain.
- APP specifically modulates mcGO movement direction through Dhc.
- The adaptor protein Sunday driver (Syd) mediates APP's effect on mcGO direction and is linked to dendritic defects.
Conclusions:
- Elucidated a model for bidirectional mcGO movement regulation.
- Revealed that APP disrupts dendritic integrity by altering mcGO directional transport via Dhc and Syd.
- Provided novel insights into the molecular pathogenesis of Alzheimer's disease at the synaptic level.
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