Abstract:
:The inner nuclear membrane (INM) is continuous with the endoplasmic reticulum (ER) but harbors a distinctive proteome essential for nuclear functions. In yeast, the Asi1/Asi2/Asi3 ubiquitin ligase complex safeguards the INM proteome through the clearance of mislocalized ER membrane proteins. How the Asi complex selectively targets mislocalized proteins and coordinates its activity with other ER functions, such as protein biogenesis, is unclear. Here, we uncover a link between INM proteome identity and membrane protein complex assembly in the remaining ER. We show that lone proteins and complex subunits failing to assemble in the ER access the INM for Asi-mediated degradation. Substrates are recognized by direct binding of Asi2 to their transmembrane domains for subsequent ubiquitination by Asi1/Asi3 and membrane extraction. Our data suggest a model in which spatial segregation of membrane protein complex assembly and quality control improves assembly efficiency and reduces the levels of orphan subunits.
journal_name
Mol Celljournal_title
Molecular cellauthors
Natarajan N,Foresti O,Wendrich K,Stein A,Carvalho Pdoi
10.1016/j.molcel.2019.10.003subject
Has Abstractpub_date
2020-01-02 00:00:00pages
108-119.e9issue
1eissn
1097-2765issn
1097-4164pii
S1097-2765(19)30763-4journal_volume
77pub_type
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