Heparan sulfate proteoglycans regulate autophagy in Drosophila

Claire E. Reynolds-Peterson, Na Zhao, Jie Xu, Taryn M. Serman, Jielin Xu, Scott B. Selleck

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Heparan sulfate-modified proteoglycans (HSPGs) are important regulators of signaling and molecular recognition at the cell surface and in the extracellular space. Disruption of HSPG core proteins, HS-synthesis, or HS-degradation can have profound effects on growth, patterning, and cell survival. The Drosophila neuromuscular junction provides a tractable model for understanding the activities of HSPGs at a synapse that displays developmental and activity-dependent plasticity. Muscle cell-specific knockdown of HS biosynthesis disrupted the organization of a specialized postsynaptic membrane, the subsynaptic reticulum (SSR), and affected the number and morphology of mitochondria. We provide evidence that these changes result from a dysregulation of macroautophagy (hereafter referred to as autophagy). Cellular and molecular markers of autophagy are all consistent with an increase in the levels of autophagy in the absence of normal HS-chain biosynthesis and modification. HS production is also required for normal levels of autophagy in the fat body, the central energy storage and nutritional sensing organ in Drosophila. Genetic mosaic analysis indicates that HS-dependent regulation of autophagy occurs non-cell autonomously, consistent with HSPGs influencing this cellular process via signaling in the extracellular space. These findings demonstrate that HS biosynthesis has important regulatory effects on autophagy and that autophagy is critical for normal assembly of postsynaptic membrane specializations.

Original languageEnglish (US)
Pages (from-to)1262-1279
Number of pages18
JournalAutophagy
Volume13
Issue number8
DOIs
StatePublished - Aug 3 2017

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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