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bioRxiv · 10.1101/2021.08.13.456248

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

Schiebel, E.·Zhang, W.·Khan, A.·Vitale, J.·Neuner, A.·Rink, K.·Luechtenborg, C.·Bruegger, B.·Soellner, T.
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Abstract

The integral membrane protein Apq12 is an important nuclear envelope (NE)/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 (AH) 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 AH is disrupted show NPC biogenesis and NE integrity defects, without impacting upon 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 AH 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 during NPC biogenesis.

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Schiebel, E., Zhang, W., Khan, A., Vitale, J., Neuner, A., Rink, K., Luechtenborg, C., Bruegger, B., Soellner, T.. 2021-08-13. A short perinuclear amphipathic α-helix in Apq12 promotes nuclear pore complex biogenesis. https://doi.org/10.1101/2021.08.13.456248

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