Details

Autor(en) / Beteiligte

• 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.

Titel

mTORC1 Controls Phase Separation and the Biophysical Properties of the Cytoplasm by Tuning Crowding

Ist Teil von

• Cell, 2018-07, Vol.174 (2), p.338-349.e20

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• 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. [Display omitted] •GEMs enable high-throughput microrheology in unperturbed living cells•mTORC1 controls diffusion by tuning ribosome concentration•Diffusion can be accurately predicted as a function of ribosome concentration•Crowding of the cytoplasm by ribosomes increases phase separation mTORC1 signaling controls phase transitions in the cytoplasm through its effects on molecular crowding.