IDEAS home Printed from https://ideas.repec.org/a/plo/pgen00/1008677.html
   My bibliography  Save this article

A Snf1-related nutrient-responsive kinase antagonizes endocytosis in yeast

Author

Listed:
  • Jessica M Tumolo
  • Nathaniel L Hepowit
  • Samika S Joshi
  • Jason A MacGurn

Abstract

Endocytosis is regulated in response to changing environmental conditions to adjust plasma membrane (PM) protein composition for optimal cell growth. Protein networks involved in cargo capture and sorting, membrane sculpting and deformation, and vesicle scission have been well-characterized, but less is known about the networks that sense extracellular cues and relay signals to trigger endocytosis of specific cargo. Hal4 and Hal5 are yeast Snf1-related kinases that were previously reported to regulate nutrient transporter stability by an unknown mechanism. Here we demonstrate that loss of Hal4 and Hal5 activates endocytosis of many different kinds of PM proteins, including Art1-mediated and Art1-independent endocytic events. Acute inhibition of Hal5 in the absence of Hal4 triggers rapid endocytosis, suggesting that Hal kinases function in a nutrient-sensing relay upstream of the endocytic response. Interestingly, Hal5 localizes to the PM, but shifts away from the cell surface in response to stimulation with specific nutrients. We propose that Hal5 functions as a nutrient-responsive regulator of PM protein stability, antagonizing endocytosis and promoting stability of endocytic cargos at the PM in nutrient-limiting conditions.Author summary: Cellular homeostasis, a fundamental requirement for all living organisms, is maintained in part through evolutionarily conserved mechanisms that regulate the abundance and activity of ion and nutrient transporters at the cell surface. These mechanisms often incorporate signaling networks that sense changes in the environment and relay signals to alter protein composition at the plasma membrane, often by inducing endocytosis of specific transporters in order to adjust and optimize transport activities at the cell surface. Here, we investigate two kinases in yeast–Hal4 and Hal5 –that are related to the yeast and human AMP sensing kinases. Loss of both Hal4 and Hal5 was previously reported to result in destabilization of ion and nutrient transporters by an unknown mechanism. Our data indicates that Hal kinases function broadly in the regulation of many different classes of endocytic cargo. Hal5 localizes to the plasma membrane in a manner that is responsive to nutrient availability and acute loss of Hal5 activity triggers rapid internalization of endocytic cargo. By uncovering a role for Hal5 as a nutrient-responsive regulator of endocytosis, this research sheds light on how signaling molecules regulate membrane trafficking events to coordinate adaptive growth responses.

Suggested Citation

  • Jessica M Tumolo & Nathaniel L Hepowit & Samika S Joshi & Jason A MacGurn, 2020. "A Snf1-related nutrient-responsive kinase antagonizes endocytosis in yeast," PLOS Genetics, Public Library of Science, vol. 16(3), pages 1-40, March.
  • Handle: RePEc:plo:pgen00:1008677
    DOI: 10.1371/journal.pgen.1008677
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1008677
    Download Restriction: no

    File URL: https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1008677&type=printable
    Download Restriction: no

    File URL: https://libkey.io/10.1371/journal.pgen.1008677?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
    ---><---

    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:plo:pgen00:1008677. 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.

    We have no bibliographic references for this item. You can help adding them by using 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: plosgenetics (email available below). General contact details of provider: https://journals.plos.org/plosgenetics/ .

    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.