Plasma membrane overgrowth causes fibrotic collagen accumulation and immune activation in Drosophila adipocytes

Abstract

Many chronic diseases are associated with fibrotic deposition of Collagen and other matrix proteins. Little is known about the factors that determine preferential onset of fibrosis in particular tissues. Here we show that plasma membrane overgrowth causes pericellular Collagen accumulation in Drosophila adipocytes. We found that loss of Dynamin and other endocytic components causes pericellular trapping of outgoing Collagen IV due to dramatic cortex expansion when endocytic removal of plasma membrane is prevented. Deposits also form in the absence of negative Toll immune regulator Cactus, excess plasma membrane being caused in this case by increased secretion. Finally, we show that trimeric Collagen accumulation, downstream of Toll or endocytic defects, activates a tissue damage response. Our work indicates that traffic imbalances and plasma membrane topology may contribute to fibrosis. It also places fibrotic deposits both downstream and upstream of immune signaling, consistent with the chronic character of fibrotic diseases.

Article and author information

Author details

  1. Yiran Zang

    School of Life Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Ming Wan

    School of Life Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Min Liu

    School of Life Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Hongmei Ke

    School of Life Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Shuangchun Ma

    School of Life Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Lu-Ping Liu

    Gene Regulatory Lab, School of Medicine, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Jian-Quan Ni

    Gene Regulatory Lab, School of Medicine, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  8. José Carlos Pastor-Pareja

    School of Life Sciences, Tsinghua University, Beijing, China
    For correspondence
    jose.pastor@biomed.tsinghua.edu.cn
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Bruno Lemaître, Ecole Polytechnique Fédérale de Lausanne, Switzerland

Version history

  1. Received: February 25, 2015
  2. Accepted: June 18, 2015
  3. Accepted Manuscript published: June 19, 2015 (version 1)
  4. Version of Record published: July 3, 2015 (version 2)

Copyright

© 2015, Zang 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

  • 4,971
    Page views
  • 938
    Downloads
  • 43
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

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. Yiran Zang
  2. Ming Wan
  3. Min Liu
  4. Hongmei Ke
  5. Shuangchun Ma
  6. Lu-Ping Liu
  7. Jian-Quan Ni
  8. José Carlos Pastor-Pareja
(2015)
Plasma membrane overgrowth causes fibrotic collagen accumulation and immune activation in Drosophila adipocytes
eLife 4:e07187.
https://doi.org/10.7554/eLife.07187

Share this article

https://doi.org/10.7554/eLife.07187

Further reading

    1. Cell Biology
    Kazuki Hanaoka, Kensuke Nishikawa ... Kouichi Funato
    Research Article

    Membrane contact sites (MCSs) are junctures that perform important roles including coordinating lipid metabolism. Previous studies have indicated that vacuolar fission/fusion processes are coupled with modifications in the membrane lipid composition. However, it has been still unclear whether MCS-mediated lipid metabolism controls the vacuolar morphology. Here, we report that deletion of tricalbins (Tcb1, Tcb2, and Tcb3), tethering proteins at endoplasmic reticulum (ER)–plasma membrane (PM) and ER–Golgi contact sites, alters fusion/fission dynamics and causes vacuolar fragmentation in the yeast Saccharomyces cerevisiae. In addition, we show that the sphingolipid precursor phytosphingosine (PHS) accumulates in tricalbin-deleted cells, triggering the vacuolar division. Detachment of the nucleus–vacuole junction (NVJ), an important contact site between the vacuole and the perinuclear ER, restored vacuolar morphology in both cells subjected to high exogenous PHS and Tcb3-deleted cells, supporting that PHS transport across the NVJ induces vacuole division. Thus, our results suggest that vacuolar morphology is maintained by MCSs through the metabolism of sphingolipids.

    1. Cell Biology
    2. Chromosomes and Gene Expression
    Monica Salinas-Pena, Elena Rebollo, Albert Jordan
    Research Article

    Histone H1 participates in chromatin condensation and regulates nuclear processes. Human somatic cells may contain up to seven histone H1 variants, although their functional heterogeneity is not fully understood. Here, we have profiled the differential nuclear distribution of the somatic H1 repertoire in human cells through imaging techniques including super-resolution microscopy. H1 variants exhibit characteristic distribution patterns in both interphase and mitosis. H1.2, H1.3, and H1.5 are universally enriched at the nuclear periphery in all cell lines analyzed and co-localize with compacted DNA. H1.0 shows a less pronounced peripheral localization, with apparent variability among different cell lines. On the other hand, H1.4 and H1X are distributed throughout the nucleus, being H1X universally enriched in high-GC regions and abundant in the nucleoli. Interestingly, H1.4 and H1.0 show a more peripheral distribution in cell lines lacking H1.3 and H1.5. The differential distribution patterns of H1 suggest specific functionalities in organizing lamina-associated domains or nucleolar activity, which is further supported by a distinct response of H1X or phosphorylated H1.4 to the inhibition of ribosomal DNA transcription. Moreover, H1 variants depletion affects chromatin structure in a variant-specific manner. Concretely, H1.2 knock-down, either alone or combined, triggers a global chromatin decompaction. Overall, imaging has allowed us to distinguish H1 variants distribution beyond the segregation in two groups denoted by previous ChIP-Seq determinations. Our results support H1 variants heterogeneity and suggest that variant-specific functionality can be shared between different cell types.