title: 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 (PM) 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 PM is prevented. Deposits also form in the absence of negative Toll immune regulator Cactus, excess PM 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 PM 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.
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Yiran
authors.initials: Y
authors.lastname: Zang
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wan
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Ke
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Shuangchun
authors.initials: S
authors.lastname: Ma
authors.affiliation: Gene Regulatory Lab, School of Medicine, Tsinghua University, Beijing, China.
authors.forename: Lu-Ping
authors.initials: LP
authors.lastname: Liu
authors.affiliation: Gene Regulatory Lab, School of Medicine, Tsinghua University, Beijing, China.
authors.forename: Jian-Quan
authors.initials: JQ
authors.lastname: Ni
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: José Carlos
authors.identifier: http://orcid.org/0000-0002-3823-4473
authors.initials: JC
authors.lastname: Pastor-Pareja
mesh_terms: D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D004330:Drosophila / Q000502:physiology*
chemical_list: D003094:Collagen
keywords: D. melanogaster; basement membrane; cell biology; extracellular matrix; immunology; membrane transport