PUBLICATION
TBC1D23 mediates Golgi-specific LKB1 signaling
- Authors
- Tu, Y., Yang, Q., Tang, M., Gao, L., Wang, Y., Wang, J., Liu, Z., Li, X., Mao, L., Jia, R.Z., Wang, Y., Tang, T.S., Xu, P., Liu, Y., Dai, L., Jia, D.
- ID
- ZDB-PUB-240228-9
- Date
- 2024
- Source
- Nature communications 15: 17851785 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- AMP-Activated Protein Kinases*/metabolism
- Animals
- Cerebellar Diseases*
- Golgi Apparatus/metabolism
- Protein Serine-Threonine Kinases/genetics
- Protein Serine-Threonine Kinases/metabolism
- Signal Transduction
- Zebrafish*/metabolism
- PubMed
- 38413626 Full text @ Nat. Commun.
Citation
Tu, Y., Yang, Q., Tang, M., Gao, L., Wang, Y., Wang, J., Liu, Z., Li, X., Mao, L., Jia, R.Z., Wang, Y., Tang, T.S., Xu, P., Liu, Y., Dai, L., Jia, D. (2024) TBC1D23 mediates Golgi-specific LKB1 signaling. Nature communications. 15:17851785.
Abstract
Liver kinase B1 (LKB1), an evolutionarily conserved serine/threonine kinase, is a master regulator of the AMPK subfamily and controls cellular events such as polarity, proliferation, and energy homeostasis. Functions and mechanisms of the LKB1-AMPK axis at specific subcellular compartments, such as lysosome and mitochondria, have been established. AMPK is known to be activated at the Golgi; however, functions and regulatory mechanisms of the LKB1-AMPK axis at the Golgi apparatus remain elusive. Here, we show that TBC1D23, a Golgi-localized protein that is frequently mutated in the neurodevelopment disorder pontocerebellar hypoplasia (PCH), is specifically required for the LKB1 signaling at the Golgi. TBC1D23 directly interacts with LKB1 and recruits LKB1 to Golgi, promoting Golgi-specific activation of AMPK upon energy stress. Notably, Golgi-targeted expression of LKB1 rescues TBC1D23 deficiency in zebrafish models. Furthermore, the loss of LKB1 causes neurodevelopmental abnormalities in zebrafish, which partially recapitulates defects in TBC1D23-deficient zebrafish, and LKB1 sustains normal neuronal development via TBC1D23 interaction. Our study uncovers a regulatory mechanism of the LKB1 signaling, and reveals that a disrupted Golgi-LKB1 signaling underlies the pathogenesis of PCH.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping