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Delarue, M.* ; Brittingham, G.P.* ; Pfeffer, S.* ; Surovtsev, I.V.* ; Pinglay, S.* ; Kennedy, K.J.* ; Schaffer, M.* ; Gutierrez, J.I.* ; Sang, D.* ; Poterewicz, G.* ; Chung, J.K.* ; Plitzko, J.M.* ; Groves, J.T.* ; Jacobs-Wagner, C.* ; Engel, B.D. ; Holt, L.J.*

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

Cell 174, 338-349.e20 (2018)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Biophysics ; Cytoplasm ; Electron Tomography ; Mtorc1 ; Microrheology ; Molecular Crowding ; Nanoparticles ; Phase Separation ; Ribosomes ; Systems Biology
ISSN (print) / ISBN 0092-8674
e-ISSN 1097-4172
Journal Cell
Quellenangaben Volume: 174, Issue: 2, Pages: 338-349.e20 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Cambridge, Mass.
Reviewing status Peer reviewed
Institute(s) Helmholtz Pioneer Campus (HPC)