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

Publication 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.

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  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
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