A mechanism for exocyst-mediated tethering via Arf6 and PIP5K1C-driven phosphoinositide conversion

Hannes Maib, David H. Murray (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    17 Citations (Scopus)
    113 Downloads (Pure)


    Polarized trafficking is necessary for the development of eukaryotes and is regulated by a conserved molecular machinery. Late steps of cargo delivery are mediated by the exocyst complex, which integrates lipid and protein components to tether vesicles for plasma membrane fusion. However, the molecular mechanisms of this process are poorly defined. Here, we reconstitute functional octameric human exocyst, demonstrating the basis for holocomplex coalescence and biochemically stable subcomplexes. We determine that each subcomplex independently binds to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), which is minimally sufficient for membrane tethering. Through reconstitution and epithelial cell biology experiments, we show that Arf6-mediated recruitment of the lipid kinase PIP5K1C rapidly converts phosphatidylinositol 4-phosphate (PI(4)P) to PI(4,5)P2, driving exocyst recruitment and membrane tethering. These results provide a molecular mechanism of exocyst-mediated tethering and a unique functional requirement for phosphoinositide signaling on late-stage vesicles in the vicinity of the plasma membrane.
    Original languageEnglish
    Pages (from-to)2821-2833.E6
    Number of pages13
    JournalCurrent Biology
    Issue number13
    Early online date23 May 2022
    Publication statusPublished - 11 Jul 2022


    Dive into the research topics of 'A mechanism for exocyst-mediated tethering via Arf6 and PIP5K1C-driven phosphoinositide conversion'. Together they form a unique fingerprint.

    Cite this