Direct PA-binding by Chm7 is required for nuclear envelope surveillance at herniations

Thaller, D.; Tong, D.; Marklew, C.; Borah, S.; Ciani, B.; Lusk, C. P.

doi:10.1101/2020.05.04.074880

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bioRxiv · 10.1101/2020.05.04.074880

Direct PA-binding by Chm7 is required for nuclear envelope surveillance at herniations

Thaller, D.·Tong, D.·Marklew, C.·Borah, S.·Ciani, B.·Lusk, C. P.

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Abstract

Mechanisms that control nuclear membrane remodeling are essential to maintain the integrity of the nucleus but remain to be fully defined. Here, we identify a phosphatidic acid (PA)-binding activity in the nuclear envelope-specific ESCRT, Chm7, in budding yeast. PA-binding is mediated through a conserved hydrophobic stretch of amino acids, which confers specific binding to the inner nuclear membrane (INM). This INM-binding is independent but nonetheless required for interaction with the LAP2-emerin-MAN1 (LEM) domain protein, Heh1 (LEM2). Consistent with the functional importance of PA-binding, mutation of this region inhibits recruitment of Chm7 to the INM and abolishes Chm7 function in the context of nuclear envelope herniations or "blebs" that form during defective nuclear pore complex (NPC) biogenesis. In fact, we show that PA accumulates at nuclear envelope herniations. We suggest that local control of PA metabolism is important for ensuring productive nuclear envelope remodeling and that its dysregulation may contribute to pathologies associated with defective NPC assembly.

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Thaller, D., Tong, D., Marklew, C., Borah, S., Ciani, B., Lusk, C. P.. 2020-05-04. Direct PA-binding by Chm7 is required for nuclear envelope surveillance at herniations. https://doi.org/10.1101/2020.05.04.074880

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