IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-31190-x.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-31190-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-31190-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Chen-Song Zhang & Simon A. Hawley & Yue Zong & Mengqi Li & Zhichao Wang & Alexander Gray & Teng Ma & Jiwen Cui & Jin-Wei Feng & Mingjiang Zhu & Yu-Qing Wu & Terytty Yang Li & Zhiyun Ye & Shu-Yong Lin , 2017. "Fructose-1,6-bisphosphate and aldolase mediate glucose sensing by AMPK," Nature, Nature, vol. 548(7665), pages 112-116, August.
    2. Mark A. Lobas & Rongkun Tao & Jun Nagai & Mira T. Kronschläger & Philip M. Borden & Jonathan S. Marvin & Loren L. Looger & Baljit S. Khakh, 2019. "A genetically encoded single-wavelength sensor for imaging cytosolic and cell surface ATP," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    3. Bing Xiao & Matthew J. Sanders & Elizabeth Underwood & Richard Heath & Faith V. Mayer & David Carmena & Chun Jing & Philip A. Walker & John F. Eccleston & Lesley F. Haire & Peter Saiu & Steven A. Howe, 2011. "Structure of mammalian AMPK and its regulation by ADP," Nature, Nature, vol. 472(7342), pages 230-233, April.
    4. Martin Pelosse & Cécile Cottet-Rousselle & Cécile M. Bidan & Aurélie Dupont & Kapil Gupta & Imre Berger & Uwe Schlattner, 2019. "Synthetic energy sensor AMPfret deciphers adenylate-dependent AMPK activation mechanism," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    5. Bing Xiao & Matthew J. Sanders & David Carmena & Nicola J. Bright & Lesley F. Haire & Elizabeth Underwood & Bhakti R. Patel & Richard B. Heath & Philip A. Walker & Stefan Hallen & Fabrizio Giordanetto, 2013. "Structural basis of AMPK regulation by small molecule activators," Nature Communications, Nature, vol. 4(1), pages 1-10, December.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Yingfeng Tu & Qin Yang & Min Tang & Li Gao & Yuanhao Wang & Jiuqiang Wang & Zhe Liu & Xiaoyu Li & Lejiao Mao & Rui zhen Jia & Yuan Wang & Tie-shan Tang & Pinglong Xu & Yan Liu & Lunzhi Dai & Da Jia, 2024. "TBC1D23 mediates Golgi-specific LKB1 signaling," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    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.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Javier Moral-Sanz & Sophronia A. Lewis & Sandy MacMillan & Marco Meloni & Heather McClafferty & Benoit Viollet & Marc Foretz & Jorge del-Pozo & A. Mark Evans, 2022. "AMPK deficiency in smooth muscles causes persistent pulmonary hypertension of the new-born and premature death," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Shannon Trombley & Jackson Powell & Pavithran Guttipatti & Andrew Matamoros & Xiaohui Lin & Tristan O’Harrow & Tobias Steinschaden & Leann Miles & Qin Wang & Shuchao Wang & Jingyun Qiu & Qingyang Li &, 2023. "Glia instruct axon regeneration via a ternary modulation of neuronal calcium channels in Drosophila," Nature Communications, Nature, vol. 14(1), pages 1-18, 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.
    4. Xinyue Mu & Trent D. Evans & Fuzhong Zhang, 2024. "ATP biosensor reveals microbial energetic dynamics and facilitates bioproduction," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    5. Zhenzhen Zi & Zhuzhen Zhang & Qiang Feng & Chiho Kim & Xu-Dong Wang & Philipp E. Scherer & Jinming Gao & Beth Levine & Yonghao Yu, 2022. "Quantitative phosphoproteomic analyses identify STK11IP as a lysosome-specific substrate of mTORC1 that regulates lysosomal acidification," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    6. Dorothy Koveal & Paul C. Rosen & Dylan J. Meyer & Carlos Manlio Díaz-García & Yongcheng Wang & Li-Heng Cai & Peter J. Chou & David A. Weitz & Gary Yellen, 2022. "A high-throughput multiparameter screen for accelerated development and optimization of soluble genetically encoded fluorescent biosensors," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    7. Yingfeng Tu & Qin Yang & Min Tang & Li Gao & Yuanhao Wang & Jiuqiang Wang & Zhe Liu & Xiaoyu Li & Lejiao Mao & Rui zhen Jia & Yuan Wang & Tie-shan Tang & Pinglong Xu & Yan Liu & Lunzhi Dai & Da Jia, 2024. "TBC1D23 mediates Golgi-specific LKB1 signaling," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    8. Elizabeth Haythorne & Matthew Lloyd & John Walsby-Tickle & Andrei I. Tarasov & Jonas Sandbrink & Idoia Portillo & Raul Terron Exposito & Gregor Sachse & Malgorzata Cyranka & Maria Rohm & Patrik Rorsma, 2022. "Altered glycolysis triggers impaired mitochondrial metabolism and mTORC1 activation in diabetic β-cells," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    9. Kibum Kim & Hee Chan Yoo & Byung Gyu Kim & Sulhee Kim & Yulseung Sung & Ina Yoon & Ya Chun Yu & Seung Joon Park & Jong Hyun Kim & Kyungjae Myung & Kwang Yeon Hwang & Sunghoon Kim & Jung Min Han, 2022. "O-GlcNAc modification of leucyl-tRNA synthetase 1 integrates leucine and glucose availability to regulate mTORC1 and the metabolic fate of leucine," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    10. Eva Crosas-Molist & Vittoria Graziani & Oscar Maiques & Pahini Pandya & Joanne Monger & Remi Samain & Samantha L. George & Saba Malik & Jerrine Salise & Valle Morales & Adrien Le Guennec & R. Andrew A, 2023. "AMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin-dependent cell migration," Nature Communications, Nature, vol. 14(1), pages 1-22, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31190-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.