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Designer membraneless organelles sequester native factors for control of cell behavior

delete2021-08-02
delete69
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OA
AI
M
Mikael V. Garabedian
W
Wentao Wang
J
Jorge Dabdoub
M
Michelle Tong
R
Reese M. Caldwell
W
William Benman
B
Benjamin S. Schuster
A
Alexander Deiters
M
Matthew C. Good *
DOI:10.1038/s41589-021-00840-4delete
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Abstract

Abstract

En 中文
Subcellular compartmentalization of macromolecules increases flux and prevents inhibitory interactions to control biochemical reactions. Inspired by this functionality, we sought to build designer compartments that function as hubs to regulate the flow of information through cellular control systems. We report a synthetic membraneless organelle platform to control endogenous cellular activities through sequestration and insulation of native proteins. We engineer and express a disordered protein scaffold to assemble micron-size condensates and recruit endogenous clients via genomic tagging with high-affinity dimerization motifs. By relocalizing up to 90% of targeted enzymes to synthetic condensates, we efficiently control cellular behaviors, including proliferation, division and cytoskeletal organization. Further, we demonstrate multiple strategies for controlled cargo release from condensates to switch cells between functional states. These synthetic organelles offer a powerful and generalizable approach to modularly control cell decision-making in a variety of model systems with broad applications for cellular engineering.
Keywords:
PHASE-TRANSITIONS
KINASE CDC5
PROTEIN
ESTABLISHMENT
SCAFFOLDS
POLARITY
ACTIVATION
SEPARATION
NUCLEUS
DOMAINS
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Journal

Nature Chemical Biology cover
Nature Chemical Biology
IF:
13.7
Papers:
4.8K
Citations:
3.3W

Organization

R
rutgers university new brunswick
Scholars:
2.3W
Papers: 1.9W
Citations: 32
R
rutgers university system
Scholars:
4.1W
Papers: 3.6W
Citations: 53
U
university of pennsylvania
Scholars:
9.2W
Papers: 7.8W
Citations: 153
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