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Citation
Guida, M.C., Hermle, T., Graham, L.A., Hauser, V., Ryan, M., Stevens, T.H., Simons, M. (2018). ATP6AP2 functions as a V-ATPase assembly factor in the endoplasmic reticulum.  Mol. Biol. Cell 29(18): 2156--2164.
FlyBase ID
FBrf0239941
Publication Type
Research paper
Abstract

ATP6AP2 (also known as the prorenin receptor) is a type I transmembrane protein that can be cleaved into two fragments in the Golgi apparatus. While in Drosophila ATP6AP2 functions in the planar cell polarity (PCP) pathway, recent human genetic studies have suggested that ATP6AP2 could participate in the assembly of the V-ATPase in the endoplasmic reticulum (ER). Using a yeast model, we show here that the V-ATPase assembly factor Voa1 can functionally be replaced by Drosophila ATP6AP2. This rescue is even more efficient when coexpressing its binding partner ATP6AP1, indicating that these two proteins together fulfill Voa1 functions in higher organisms. Structure-function analyses in both yeast and Drosophila show that proteolytic cleavage is dispensable, while C-terminus-dependent ER retrieval is required for ATP6AP2 function. Accordingly, we demonstrate that both overexpression and lack of ATP6AP2 causes ER stress in Drosophila wing cells and that the induction of ER stress is sufficient to cause PCP phenotypes. In summary, our results suggest that full-length ATP6AP2 contributes to the assembly of the V-ATPase proton pore and that impairment of this function affects ER homeostasis and PCP signaling.

PubMed ID
PubMed Central ID
PMC6249795 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Mol. Biol. Cell
    Title
    Molecular Biology of the Cell
    Publication Year
    1992-
    ISBN/ISSN
    1059-1524
    Data From Reference
    Genes (4)