TBC1D23 mediates Golgi-specific LKB1 signaling
Yingfeng Tu1, Qin Yang1, Min Tang1
1Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, 610041, China.
Nature Communications
|February 27, 2024
Summary
The TBC1D23 protein is crucial for Liver kinase B1 (LKB1) signaling at the Golgi apparatus, impacting energy homeostasis and neuronal development. Its disruption causes pontocerebellar hypoplasia (PCH).
Area of Science:
- Cell Biology
- Neuroscience
- Molecular Biology
Background:
- Liver kinase B1 (LKB1) regulates cellular energy and polarity via the AMPK pathway.
- LKB1-AMPK signaling is known in mitochondria and lysosomes, but its Golgi function is unclear.
- TBC1D23 mutations cause pontocerebellar hypoplasia (PCH), a neurodevelopmental disorder.
Purpose of the Study:
- To investigate the role of the LKB1-AMPK axis at the Golgi apparatus.
- To elucidate the function of TBC1D23 in LKB1 signaling and its link to PCH.
Main Methods:
- Investigated protein interactions between TBC1D23 and LKB1.
- Utilized zebrafish models to study LKB1 and TBC1D23 function in vivo.
- Examined Golgi-specific AMPK activation under energy stress.
Main Results:
- TBC1D23 directly binds and recruits LKB1 to the Golgi.
- TBC1D23 is essential for Golgi-specific AMPK activation during energy stress.
- Targeted LKB1 expression in the Golgi rescues TBC1D23 deficiency in zebrafish.
- LKB1 loss causes neurodevelopmental defects in zebrafish, mimicking TBC1D23 deficiency.
Conclusions:
- TBC1D23 is a key regulator of Golgi-localized LKB1 signaling.
- Disrupted Golgi-LKB1 signaling contributes to the pathogenesis of PCH.
- LKB1-TBC1D23 interaction is vital for normal neuronal development.
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