IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-29503-1.html
   My bibliography  Save this article

The PripA-TbcrA complex-centered Rab GAP cascade facilitates macropinosome maturation in Dictyostelium

Author

Listed:
  • Hui Tu

    (Institute of Biophysics, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Zhimeng Wang

    (Institute of Biophysics, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Ye Yuan

    (Institute of Biophysics, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Xilin Miao

    (Institute of Biophysics, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Dong Li

    (Institute of Biophysics, Chinese Academy of Sciences
    University of Science and Technology of China)

  • Hu Guo

    (Institute of Biophysics, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Yihong Yang

    (Institute of Biophysics, Chinese Academy of Sciences)

  • Huaqing Cai

    (Institute of Biophysics, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

Abstract

Macropinocytosis, an evolutionarily conserved mechanism mediating nonspecific bulk uptake of extracellular fluid, has been ascribed diverse functions. How nascent macropinosomes mature after internalization remains largely unknown. By searching for proteins that localize on macropinosomes during the Rab5-to-Rab7 transition stage in Dictyostelium, we uncover a complex composed of two proteins, which we name PripA and TbcrA. We show that the Rab5-to-Rab7 conversion involves fusion of Rab5-marked early macropinosomes with Rab7-marked late macropinosomes. PripA links the two membrane compartments by interacting with PI(3,4)P2 and Rab7. In addition, PripA recruits TbcrA, which acts as a GAP, to turn off Rab5. Thus, the conversion to Rab7 is linked to inactivation of the upstream Rab5. Consistently, disruption of either pripA or tbcrA impairs Rab5 inactivation and macropinocytic cargo processing. Therefore, the PripA-TbcrA complex is the central component of a Rab GAP cascade that facilitates programmed Rab switch and efficient cargo trafficking during macropinosome maturation.

Suggested Citation

  • Hui Tu & Zhimeng Wang & Ye Yuan & Xilin Miao & Dong Li & Hu Guo & Yihong Yang & Huaqing Cai, 2022. "The PripA-TbcrA complex-centered Rab GAP cascade facilitates macropinosome maturation in Dictyostelium," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29503-1
    DOI: 10.1038/s41467-022-29503-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-29503-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-29503-1?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. Cosimo Commisso & Shawn M. Davidson & Rengin G. Soydaner-Azeloglu & Seth J. Parker & Jurre J. Kamphorst & Sean Hackett & Elda Grabocka & Michel Nofal & Jeffrey A. Drebin & Craig B. Thompson & Joshua D, 2013. "Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells," Nature, Nature, vol. 497(7451), pages 633-637, May.
    2. Jason M. Kinchen & Kodi S. Ravichandran, 2010. "Identification of two evolutionarily conserved genes regulating processing of engulfed apoptotic cells," Nature, Nature, vol. 464(7289), pages 778-782, April.
    3. Anne Simonsen & Roger Lippe & Savvas Christoforidis & Jean-Michel Gaullier & Andreas Brech & Judy Callaghan & Ban-Hock Toh & Carol Murphy & Marino Zerial & Harald Stenmark, 1998. "EEA1 links PI(3)K function to Rab5 regulation of endosome fusion," Nature, Nature, vol. 394(6692), pages 494-498, July.
    Full references (including those not matched with items on IDEAS)

    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. Oliver M Crook & Aikaterini Geladaki & Daniel J H Nightingale & Owen L Vennard & Kathryn S Lilley & Laurent Gatto & Paul D W Kirk, 2020. "A semi-supervised Bayesian approach for simultaneous protein sub-cellular localisation assignment and novelty detection," PLOS Computational Biology, Public Library of Science, vol. 16(11), pages 1-21, November.
    2. David Paul & Omer Stern & Yvonne Vallis & Jatinder Dhillon & Andrew Buchanan & Harvey McMahon, 2023. "Cell surface protein aggregation triggers endocytosis to maintain plasma membrane proteostasis," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Eva Maria Wenzel & Nina Marie Pedersen & Liv Anker Elfmark & Ling Wang & Ingrid Kjos & Espen Stang & Lene Malerød & Andreas Brech & Harald Stenmark & Camilla Raiborg, 2024. "Intercellular transfer of cancer cell invasiveness via endosome-mediated protease shedding," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    4. Ella N. Hoogenboezem & Shrusti S. Patel & Justin H. Lo & Ashley B. Cavnar & Lauren M. Babb & Nora Francini & Eva F. Gbur & Prarthana Patil & Juan M. Colazo & Danielle L. Michell & Violeta M. Sanchez &, 2024. "Structural optimization of siRNA conjugates for albumin binding achieves effective MCL1-directed cancer therapy," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    5. Edoardo Ratto & S. Roy Chowdhury & Nora S. Siefert & Martin Schneider & Marten Wittmann & Dominic Helm & Wilhelm Palm, 2022. "Direct control of lysosomal catabolic activity by mTORC1 through regulation of V-ATPase assembly," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Misty Shuo Zhang & Jane Di Cui & Derek Lee & Vincent Wai-Hin Yuen & David Kung-Chun Chiu & Chi Ching Goh & Jacinth Wing-Sum Cheu & Aki Pui-Wah Tse & Macus Hao-Ran Bao & Bowie Po Yee Wong & Carrie Yili, 2022. "Hypoxia-induced macropinocytosis represents a metabolic route for liver cancer," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    7. Kay Oliver Schink & Kia Wee Tan & Hélène Spangenberg & Domenica Martorana & Marte Sneeggen & Virginie Stévenin & Jost Enninga & Coen Campsteijn & Camilla Raiborg & Harald Stenmark, 2021. "The phosphoinositide coincidence detector Phafin2 promotes macropinocytosis by coordinating actin organisation at forming macropinosomes," Nature Communications, Nature, vol. 12(1), pages 1-17, 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_s41467-022-29503-1. 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.