mTORC1 controls phase separation and the biophysical properties of the cytoplasm by tuning crowding

Delarue, M. and Brittingham, G. P. and Pfeffer, S. and Surovtsev, I. V. and Pinglay, S. and Kennedy, K. J. and Schaffer, M. and Gutierrez, J. I. and Sang, D. and Poterewicz, G. and Chung, J. K. and Plitzko, J. M. and Groves, J. T. and Jacobs-Wagner, C. and Engel, B. D. and Holt, L. J.. (2018) mTORC1 controls phase separation and the biophysical properties of the cytoplasm by tuning crowding. Cell, 174 (2). pp. 338-349.e20.

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Official URL: https://edoc.unibas.ch/89555/

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Macromolecular crowding has a profound impact on reaction rates and the physical properties of the cell interior, but the mechanisms that regulate crowding are poorly understood. We developed genetically encoded multimeric nanoparticles (GEMs) to dissect these mechanisms. GEMs are homomultimeric scaffolds fused to a fluorescent protein that self-assemble into bright, stable particles of defined size and shape. By combining tracking of GEMs with genetic and pharmacological approaches, we discovered that the mTORC1 pathway can modulate the effective diffusion coefficient of particles ≥20 nm in diameter more than 2-fold by tuning ribosome concentration, without any discernable effect on the motion of molecules ≤5 nm. This change in ribosome concentration affected phase separation both in vitro and in vivo. Together, these results establish a role for mTORC1 in controlling both the mesoscale biophysical properties of the cytoplasm and biomolecular condensation.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology and Biophysics (Engel)
UniBasel Contributors:Engel, Ben
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Cell Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:29 Aug 2022 15:57
Deposited On:23 Aug 2022 08:59

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