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Synuclein plasma membrane localization correlates with cellular phosphatidylinositol polyphosphate levels

eLife, 2021-02, Vol.10 [Peer Reviewed Journal]

COPYRIGHT 2021 eLife Science Publications, Ltd. ;ISSN: 2050-084X ;EISSN: 2050-084X ;DOI: 10.7554/eLife.61951

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  • Title:
    Synuclein plasma membrane localization correlates with cellular phosphatidylinositol polyphosphate levels
  • Author: Jacob, Reeba Susan ; Eichmann, Cédric ; Dema, Alessandro ; Mercadante, Davide ; Selenko, Philipp
  • Subjects: Cell membranes ; Lipids ; Phosphatases
  • Is Part Of: eLife, 2021-02, Vol.10
  • Description: The Parkinson's disease protein [alpha]-synuclein ([alpha]Syn) promotes membrane fusion and fission by interacting with various negatively charged phospholipids. Despite postulated roles in endocytosis and exocytosis, plasma membrane (PM) interactions of [alpha]Syn are poorly understood. Here, we show that phosphatidylinositol 4,5-bisphosphate (PIP.sub.2) and phosphatidylinositol 3,4,5-trisphosphate (PIP.sub.3), two highly acidic components of inner PM leaflets, mediate PM localization of endogenous pools of [alpha]Syn in A2780, HeLa, SK-MEL-2, and differentiated and undifferentiated neuronal SH-SY5Y cells. We demonstrate that [alpha]Syn binds to reconstituted PIP.sub.2 membranes in a helical conformation in vitro and that PIP.sub.2 synthesizing kinases and hydrolyzing phosphatases reversibly redistribute [alpha]Syn in cells. We further delineate that [alpha]Syn-PM targeting follows phosphoinositide-3 kinase (PI3K)-dependent changes of cellular PIP.sub.2 and PIP.sub.3 levels, which collectively suggests that phosphatidylinositol polyphosphates contribute to [alpha]Syn's function(s) at the plasma membrane.
  • Publisher: eLife Science Publications, Ltd
  • Language: English
  • Identifier: ISSN: 2050-084X
    EISSN: 2050-084X
    DOI: 10.7554/eLife.61951
  • Source: Open Access: PubMed Central
    AUTh Library subscriptions: ProQuest Central
    ROAD: Directory of Open Access Scholarly Resources
    DOAJ Directory of Open Access Journals
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