Phase Separation: Linking Cellular Compartmentalization to Disease

Eukaryotic cells are complex structures capable of coordinating numerous biochemical reactions in space and time. Key to such coordination is the subdivision of intracellular space into functional compartments. Compartmentalization can be achieved by intracellular membranes, which surround organelle...

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Bibliographic Details
Published in:Trends in cell biology Vol. 26; no. 7; pp. 547 - 558
Main Authors: Aguzzi, Adriano, Altmeyer, Matthias
Format: Journal Article
Language:English
Published: England Elsevier Ltd 01.07.2016
Subjects:
Animals
Cell Compartmentation
Disease
Eukaryotic Cells - metabolism
Humans
intrinsically disordered proteins
liquid demixing
low-complexity domains
neurodegeneration
Pathology
Phase Transition
protein assembly and aggregation
Proteins - metabolism
neurodegeneration
phase transition
intrinsically disordered proteins
liquid demixing
low-complexity domains
protein assembly and aggregation
ISSN:0962-8924, 1879-3088
Online Access:Get full text
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Summary:Eukaryotic cells are complex structures capable of coordinating numerous biochemical reactions in space and time. Key to such coordination is the subdivision of intracellular space into functional compartments. Compartmentalization can be achieved by intracellular membranes, which surround organelles and act as physical barriers. In addition, cells have developed sophisticated mechanisms to partition their inner substance in a tightly regulated manner. Recent studies provide compelling evidence that membraneless compartmentalization can be achieved by liquid demixing, a process culminating in liquid–liquid phase separation and the formation of phase boundaries. We discuss how this emerging concept may help in understanding dynamic reorganization of subcellular space and highlight its potential as a framework to explain pathological protein assembly in cancer and neurodegeneration. Membraneless compartmentalization of the subcellular space occurs by liquid–liquid phase separation. Heterotypic cooperative weak interactions enable rapid rearrangements within liquid compartments. Intrinsically disordered proteins play important roles in phase transitions due to their structural plasticity and prion-like properties. Cells dynamically control the extent and duration of phase transitions. Molecular seeds such as RNA or poly(ADP-ribose) (PAR) can trigger phase transitions in a stimulus- and context-specific manner. Chaperones, disintegrase machineries, and post-translational modifications cooperate to control phase transitions. A continuum of aggregation propensities exists and cells employ an unanticipated broad range of material states in proteinaceous assemblies. These can progress into pathological aggregates associated with neurodegenerative diseases.
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ISSN:0962-8924
1879-3088
DOI:10.1016/j.tcb.2016.03.004