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bioRxiv · 10.1101/2021.01.28.428001

Nodal modulator is required to sustain endoplasmic reticulum morphology

Amaya, C.·Cameron, C. J.·Devarkar, S. C.·Gerstein, M. B.·Xiong, Y.·Schlieker, C.
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Abstract

Nodal Modulator (NOMO) is a widely conserved type I transmembrane protein of unknown function, with three nearly identical orthologs specified in the human genome. We identified NOMO1 in a proteomics approach aimed at the identification of proteins that support the structural integrity of the endoplasmic reticulum (ER). Overexpression of NOMO1 imposes a sheet morphology on the ER, while depletion of NOMO1 and its orthologs causes a collapse of ER morphology concomitant with the formation of membrane-delineated holes in the ER network. These structures are positive for the autophagy marker LAMP1, and LC3 is profoundly upregulated upon NOMO depletion. In vitro reconstitution of NOMO1 revealed a dimeric state that is mediated by the cytosolic tail domain, with each monomer featuring a "beads on a string" structure likely representing bacterial Ig-like folds. Based on these observations and a genetic epistasis analysis including the known ER-shaping proteins Atlastin2 and Climp63, we propose a role for NOMO1 in the functional network of ER-shaping proteins.

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Amaya, C., Cameron, C. J., Devarkar, S. C., Gerstein, M. B., Xiong, Y., Schlieker, C.. 2021-01-28. Nodal modulator is required to sustain endoplasmic reticulum morphology. https://doi.org/10.1101/2021.01.28.428001

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