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Pleiner, T.; Hazu, M.; Pinton Tomaleri, G.; Januszyk, K.; Oania, R.S.; Sweredoski, M.J.; Moradian, A.; Guna, A.; Voorhees, R.M. (2021) WNK1 is an assembly factor for the human ER membrane protein complex. Mol. Cell, 81, 2693-2704.e12.

WNK1 graphical abstract-01_edited.jpg

We discovered that the essential kinase WNK1 moonlights as an EMC assembly factor and characterized its requirement using in vitro reconstitution and cell-based stability assays. We found that WNK1 uses a conserved amphipathic helix to prevent premature degradation of the newly synthesized subunit EMC2 by shielding an exposed hydrophobic interface. WNK1’s role in EMC assembly revealed several properties of an assembly factor that will apply broadly across the proteome. Given WNK1’s primary function in controlling ion homeostasis, especially in response to osmotic stress, our new findings imply an intriguing connection between EMC assembly and cellular stress pathways.

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