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Spatial regulation of AMPK signaling revealed by a sensitive kinase activity reporter

Author

Listed:
  • Danielle L. Schmitt

    (University of California San Diego)

  • Stephanie D. Curtis

    (The Salk Institute for Biological Studies)

  • Anne C. Lyons

    (University of California San Diego)

  • Jin-fan Zhang

    (University of California San Diego)

  • Mingyuan Chen

    (University of California San Diego)

  • Catherine Y. He

    (University of California San Diego)

  • Sohum Mehta

    (University of California San Diego)

  • Reuben J. Shaw

    (The Salk Institute for Biological Studies)

  • Jin Zhang

    (University of California San Diego
    University of California San Diego
    University of California San Diego)

Abstract

AMP-activated protein kinase (AMPK) is a master regulator of cellular energetics which coordinates metabolism by phosphorylating a plethora of substrates throughout the cell. But how AMPK activity is regulated at different subcellular locations for precise spatiotemporal control over metabolism is unclear. Here we present a sensitive, single-fluorophore AMPK activity reporter (ExRai AMPKAR), which reveals distinct kinetic profiles of AMPK activity at the mitochondria, lysosome, and cytoplasm. Genetic deletion of the canonical upstream kinase liver kinase B1 (LKB1) results in slower AMPK activity at lysosomes but does not affect the response amplitude at lysosomes or mitochondria, in sharp contrast to the necessity of LKB1 for maximal cytoplasmic AMPK activity. We further identify a mechanism for AMPK activity in the nucleus, which results from cytoplasmic to nuclear shuttling of AMPK. Thus, ExRai AMPKAR enables illumination of the complex subcellular regulation of AMPK signaling.

Suggested Citation

  • Danielle L. Schmitt & Stephanie D. Curtis & Anne C. Lyons & Jin-fan Zhang & Mingyuan Chen & Catherine Y. He & Sohum Mehta & Reuben J. Shaw & Jin Zhang, 2022. "Spatial regulation of AMPK signaling revealed by a sensitive kinase activity reporter," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31190-x
    DOI: 10.1038/s41467-022-31190-x
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    References listed on IDEAS

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    2. Wei Lin & Abhishek Phatarphekar & Yanghao Zhong & Longwei Liu & Hyung-Bae Kwon & William H. Gerwick & Yingxiao Wang & Sohum Mehta & Jin Zhang, 2024. "Light-gated integrator for highlighting kinase activity in living cells," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Yaqiong Li & Zhipeng Niu & Jichao Yang & Xuke Yang & Yukun Chen & Yingying Li & Xiaohan Liang & Jingwen Zhang & Fuqiang Fan & Ping Wu & Chao Peng & Bang Shen, 2023. "Rapid metabolic reprogramming mediated by the AMP-activated protein kinase during the lytic cycle of Toxoplasma gondii," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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