Abstracts


Morphogenesis of complex membrane structures: Endoplasmic Reticulum stacks and whorls

Presenting author: Natalie Friemel

Heidelberg University Biochemistry Center, , Im Neuenheimer Feld 328, 69120 Heidelberg [DE],

Author(s):
Natalie Friemel, Sebastian Schuck

Cells dynamically remodel the morphology of their organelles to optimise organelle function. The endoplasmic reticulum (ER) membrane can be shaped into arrays of sheets that form flat stacks or spherical whorls. ER stacks and whorls can have distinctive protein compositions and may support protein maturation, drug detoxification or autophagy. The molecular machinery for the formation of these ER subdomains and their precise membrane topology remain unknown. Here, we employ subdomains induced by the ER membrane protein Hmg2 as a model for ER morphogenesis in yeast. We combine a genetic screen, spatial proteomics and cryo-electron tomography to identify factors in stack and whorl formation and define their three-dimensional architecture. We find that the transition from flat sheets to spherical ER structures depends on membrane abundance and rim stabilisation by reticulon proteins. Additionally, certain lumenal and membrane-associated ER proteins are excluded from stacks and whorls, suggesting a protein sorting mechanism during ER subdomain formation. This selectivity may be based on protein size because stacked smooth ER sheets are about 40% thinner than rough ER sheets and thus offer less lumenal space. Overall, understanding the molecular mechanisms of ER morphogenesis will help to further define the relationship between organelle form and function.

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