IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-26775-x.html
   My bibliography  Save this article

The phosphoinositide coincidence detector Phafin2 promotes macropinocytosis by coordinating actin organisation at forming macropinosomes

Author

Listed:
  • Kay Oliver Schink

    (University of Oslo, Montebello
    Institute for Cancer Research, Oslo University Hospital, Montebello)

  • Kia Wee Tan

    (University of Oslo, Montebello
    Institute for Cancer Research, Oslo University Hospital, Montebello)

  • Hélène Spangenberg

    (University of Oslo, Montebello
    Institute for Cancer Research, Oslo University Hospital, Montebello)

  • Domenica Martorana

    (University of Oslo, Montebello
    Institute for Cancer Research, Oslo University Hospital, Montebello)

  • Marte Sneeggen

    (University of Oslo, Montebello
    Institute for Cancer Research, Oslo University Hospital, Montebello)

  • Virginie Stévenin

    (Leiden University Medical Center
    Institut Pasteur, Dynamics of Host-Pathogen Interactions Unit)

  • Jost Enninga

    (Institut Pasteur, Dynamics of Host-Pathogen Interactions Unit)

  • Coen Campsteijn

    (Institute of Basic Medical Sciences, University of Oslo)

  • Camilla Raiborg

    (University of Oslo, Montebello
    Institute for Cancer Research, Oslo University Hospital, Montebello)

  • Harald Stenmark

    (University of Oslo, Montebello
    Institute for Cancer Research, Oslo University Hospital, Montebello)

Abstract

Uptake of large volumes of extracellular fluid by actin-dependent macropinocytosis has an important role in infection, immunity and cancer development. A key question is how actin assembly and disassembly are coordinated around macropinosomes to allow them to form and subsequently pass through the dense actin network underlying the plasma membrane to move towards the cell center for maturation. Here we show that the PH and FYVE domain protein Phafin2 is recruited transiently to newly-formed macropinosomes by a mechanism that involves coincidence detection of PtdIns3P and PtdIns4P. Phafin2 also interacts with actin via its PH domain, and recruitment of Phafin2 coincides with actin reorganization around nascent macropinosomes. Moreover, forced relocalization of Phafin2 to the plasma membrane causes rearrangement of the subcortical actin cytoskeleton. Depletion of Phafin2 inhibits macropinosome internalization and maturation and prevents KRAS-transformed cancer cells from utilizing extracellular protein as an amino acid source. We conclude that Phafin2 promotes macropinocytosis by controlling timely delamination of actin from nascent macropinosomes for their navigation through the dense subcortical actin network.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26775-x
    DOI: 10.1038/s41467-021-26775-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-26775-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-26775-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. Craig Ramirez & Andrew D. Hauser & Emily A. Vucic & Dafna Bar-Sagi, 2019. "Plasma membrane V-ATPase controls oncogenic RAS-induced macropinocytosis," Nature, Nature, vol. 576(7787), pages 477-481, December.
    2. 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.
    3. Kangmin He & Robert Marsland III & Srigokul Upadhyayula & Eli Song & Song Dang & Benjamin R. Capraro & Weiming Wang & Wesley Skillern & Raphael Gaudin & Minghe Ma & Tom Kirchhausen, 2017. "Dynamics of phosphoinositide conversion in clathrin-mediated endocytic traffic," Nature, Nature, vol. 552(7685), pages 410-414, December.
    4. Marte Sneeggen & Nina Marie Pedersen & Coen Campsteijn & Ellen Margrethe Haugsten & Harald Stenmark & Kay Oliver Schink, 2019. "WDFY2 restrains matrix metalloproteinase secretion and cell invasion by controlling VAMP3-dependent recycling," Nature Communications, Nature, vol. 10(1), pages 1-20, December.
    5. Sarah R. Barger & Nicholas S. Reilly & Maria S. Shutova & Qingsen Li & Paolo Maiuri & John M. Heddleston & Mark S. Mooseker & Richard A. Flavell & Tatyana Svitkina & Patrick W. Oakes & Mira Krendel & , 2019. "Membrane-cytoskeletal crosstalk mediated by myosin-I regulates adhesion turnover during phagocytosis," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    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. 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.
    2. Raluca Groza & Kita Valerie Schmidt & Paul Markus Müller & Paolo Ronchi & Claire Schlack-Leigers & Ursula Neu & Dmytro Puchkov & Rumiana Dimova & Claudia Matthaeus & Justin Taraska & Thomas R. Weikl &, 2024. "Adhesion energy controls lipid binding-mediated endocytosis," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. 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.
    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. 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.
    7. Tatsat Banerjee & Satomi Matsuoka & Debojyoti Biswas & Yuchuan Miao & Dhiman Sankar Pal & Yoichiro Kamimura & Masahiro Ueda & Peter N. Devreotes & Pablo A. Iglesias, 2023. "A dynamic partitioning mechanism polarizes membrane protein distribution," Nature Communications, Nature, vol. 14(1), pages 1-24, 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:12:y:2021:i:1:d:10.1038_s41467-021-26775-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.