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
  • Animals
  • Cerebellar Diseases*
  • AMP-Activated Protein Kinases*/metabolism
  • Golgi Apparatus/metabolism
  • Zebrafish*/metabolism
  • Signal Transduction
  • Protein Serine-Threonine Kinases/genetics
  • Protein Serine-Threonine Kinases/metabolism
(all 8)
PubMed
38413626 Full text @ Nat. Commun.
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
Figures
Figure Gallery (8 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
knu3Tg + MO1-tbc1d23standard conditionsLong-pec
knu3Tg + MO2-stk11standard conditionsLong-pec
ml2Tg + MO1-tbc1d23standard conditionsLong-pec
ml2Tg + MO2-stk11standard conditionsLong-pec
1 - 4 of 4
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
knu3TgTransgenic Insertion
    ml2TgTransgenic Insertion
      1 - 2 of 2
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      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      Target Reagent Reagent Type
      stk11MO2-stk11MRPHLNO
      tbc1d23MO1-tbc1d23MRPHLNO
      1 - 2 of 2
      Show
      Fish
      Fish
      knu3Tg + MO1-tbc1d23
      knu3Tg + MO2-stk11
      ml2Tg + MO1-tbc1d23
      ml2Tg + MO2-stk11
      1 - 4 of 4
      Show
      Antibodies
      No data available
      Orthology
      No data available
      Engineered Foreign Genes
      Marker Marker Type Name
      EGFPEFGEGFP
      GFPEFGGFP
      1 - 2 of 2
      Show
      Mapping
      No data available
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      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.