Abstract

Yeast studies identified two heterohexameric tethering complexes, which consist of 4 shared (Vps11, Vps16, Vps18 and Vps33) and 2 specific subunits: Vps3 and Vps8 (CORVET) versus Vps39 and Vps41 (HOPS). CORVET is an early and HOPS is a late endosomal tether. The function of HOPS is well known in animal cells, while CORVET is poorly characterized. Here we show that Drosophila Vps8 is highly expressed in hemocytes and nephrocytes, and localizes to early endosomes despite the lack of a clear Vps3 homolog. We find that Vps8 forms a complex and acts together with Vps16A, Dor/Vps18 and Car/Vps33A, and loss of any of these proteins leads to fragmentation of endosomes. Surprisingly, Vps11 deletion causes enlargement of endosomes, similar to loss of the HOPS-specific subunits Vps39 and Lt/Vps41. We thus identify a 4 subunit-containing miniCORVET complex as an unconventional early endosomal tether in Drosophila.

Article and author information

Author details

  1. Péter Lőrincz

    Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  2. Zsolt Lakatos

    Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  3. Ágnes Varga

    Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  4. Tamás Maruzs

    Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  5. Zsófia Simon-Vecsei

    Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  6. Zsuzsanna Darula

    Laboratory of Proteomics Research, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  7. Péter Benkő

    Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  8. Gábor Csordás

    Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  9. Mónika Lippai

    Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  10. István Andó

    Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  11. Krisztina Hegedűs

    Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  12. Katalin F Medzihradszky

    Laboratory of Proteomics Research, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  13. Szabolcs Takáts

    Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  14. Gábor Juhász

    Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary
    For correspondence
    szmrt@elte.hu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Randy Schekman, Howard Hughes Medical Institute, University of California, Berkeley, United States

Version history

  1. Received: January 6, 2016
  2. Accepted: June 1, 2016
  3. Accepted Manuscript published: June 2, 2016 (version 1)
  4. Version of Record published: July 6, 2016 (version 2)

Copyright

© 2016, Lőrincz et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,728
    views
  • 544
    downloads
  • 48
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Péter Lőrincz
  2. Zsolt Lakatos
  3. Ágnes Varga
  4. Tamás Maruzs
  5. Zsófia Simon-Vecsei
  6. Zsuzsanna Darula
  7. Péter Benkő
  8. Gábor Csordás
  9. Mónika Lippai
  10. István Andó
  11. Krisztina Hegedűs
  12. Katalin F Medzihradszky
  13. Szabolcs Takáts
  14. Gábor Juhász
(2016)
MiniCORVET is a Vps8-containing early endosomal tether in Drosophila
eLife 5:e14226.
https://doi.org/10.7554/eLife.14226

Share this article

https://doi.org/10.7554/eLife.14226

Further reading

    1. Cell Biology
    Gang Liu, Yunxuan Hou ... Xiumei Jiang
    Research Article

    Erythropoiesis and megakaryopoiesis are stringently regulated by signaling pathways. However, the precise molecular mechanisms through which signaling pathways regulate key transcription factors controlling erythropoiesis and megakaryopoiesis remain partially understood. Herein, we identified heat shock cognate B (HSCB), which is well known for its iron–sulfur cluster delivery function, as an indispensable protein for friend of GATA 1 (FOG1) nuclear translocation during erythropoiesis of K562 human erythroleukemia cells and cord-blood-derived human CD34+CD90+hematopoietic stem cells (HSCs), as well as during megakaryopoiesis of the CD34+CD90+HSCs. Mechanistically, HSCB could be phosphorylated by phosphoinositol-3-kinase (PI3K) to bind with and mediate the proteasomal degradation of transforming acidic coiled-coil containing protein 3 (TACC3), which otherwise detained FOG1 in the cytoplasm, thereby facilitating FOG1 nuclear translocation. Given that PI3K is activated during both erythropoiesis and megakaryopoiesis, and that FOG1 is a key transcription factor for these processes, our findings elucidate an important, previously unrecognized iron–sulfur cluster delivery independent function of HSCB in erythropoiesis and megakaryopoiesis.

    1. Biochemistry and Chemical Biology
    2. Cell Biology
    Christopher TA Lewis, Elise G Melhedegaard ... Julien Ochala
    Research Article

    Hibernation is a period of metabolic suppression utilized by many small and large mammal species to survive during winter periods. As the underlying cellular and molecular mechanisms remain incompletely understood, our study aimed to determine whether skeletal muscle myosin and its metabolic efficiency undergo alterations during hibernation to optimize energy utilization. We isolated muscle fibers from small hibernators, Ictidomys tridecemlineatus and Eliomys quercinus and larger hibernators, Ursus arctos and Ursus americanus. We then conducted loaded Mant-ATP chase experiments alongside X-ray diffraction to measure resting myosin dynamics and its ATP demand. In parallel, we performed multiple proteomics analyses. Our results showed a preservation of myosin structure in U. arctos and U. americanus during hibernation, whilst in I. tridecemlineatus and E. quercinus, changes in myosin metabolic states during torpor unexpectedly led to higher levels in energy expenditure of type II, fast-twitch muscle fibers at ambient lab temperatures (20 °C). Upon repeating loaded Mant-ATP chase experiments at 8 °C (near the body temperature of torpid animals), we found that myosin ATP consumption in type II muscle fibers was reduced by 77–107% during torpor compared to active periods. Additionally, we observed Myh2 hyper-phosphorylation during torpor in I. tridecemilineatus, which was predicted to stabilize the myosin molecule. This may act as a potential molecular mechanism mitigating myosin-associated increases in skeletal muscle energy expenditure during periods of torpor in response to cold exposure. Altogether, we demonstrate that resting myosin is altered in hibernating mammals, contributing to significant changes to the ATP consumption of skeletal muscle. Additionally, we observe that it is further altered in response to cold exposure and highlight myosin as a potentially contributor to skeletal muscle non-shivering thermogenesis.