A short perinuclear amphipathic ?-helix in Apq12 promotes nuclear pore complex biogenesis.

The integral membrane protein Apq12 is an important nuclear envelope (NE)/endoplasmic reticulum (ER) modulator that cooperates with the nuclear pore complex (NPC) biogenesis factors Brl1 and Brr6. How Apq12 executes these functions is unknown. Here, we identified a short amphipathic ?-helix (A?H) in Apq12 that links the two transmembrane domains ...
in the perinuclear space and has liposome-binding properties. Cells expressing an APQ12 (apq12-ah) version in which A?H is disrupted show NPC biogenesis and NE integrity defects, without impacting Apq12-ah topology or NE/ER localization. Overexpression of APQ12 but not apq12-ah triggers striking over-proliferation of the outer nuclear membrane (ONM)/ER and promotes accumulation of phosphatidic acid (PA) at the NE. Apq12 and Apq12-ah both associate with NPC biogenesis intermediates and removal of A?H increases both Brl1 levels and the interaction between Brl1 and Brr6. We conclude that the short amphipathic ?-helix of Apq12 regulates the function of Brl1 and Brr6 and promotes PA accumulation at the NE possibly during NPC biogenesis.
Mesh Terms:
Membrane Proteins, Mutation, Nuclear Envelope, Nuclear Pore, Phosphatidic Acids, Protein Conformation, alpha-Helical, Protein Domains, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
Open Biol
Date: Dec. 01, 2020
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