Phase separation in biology; functional organization of a higher order

By Diana M. Mitrea, Richard W. Kriwacki. Cell Communication and Signaling, 2016

648 citations recorded by the source corpus.

Inside eukaryotic cells, macromolecules are partitioned into membrane-bounded compartments and, within these, some are further organized into non-membrane-bounded structures termed membrane-less organelles. The latter structures are comprised of heterogeneous mixtures of proteins and nucleic acids and assemble through a phase separation phenomenon similar to polymer condensation. Membrane-less organelles are dynamic structures maintained through multivalent interactions that mediate diverse biological processes, many involved in RNA metabolism. They rapidly exchange components with the cellular milieu and their properties are readily altered in response to environmental cues, often implicating membrane-less organelles in responses to stress signaling. In this review, we discuss: (1) the functional roles of membrane-less organelles, (2) unifying structural and mechanistic principles that underlie their assembly and disassembly, and (3) established and emerging methods used in structural investigations of membrane-less organelles.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/51d3b0a3c02f5d46398427aecc06706121cf146b

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Citations in the corpus

Tau protein liquid–liquid phase separation can initiate tau aggregation (2018, positive): “…intracellular gradients of RNA transcription (Brangwynne et al , 2009), the enrichment of RNA binding proteins in stress granules (Lin et al , 2015; Molliex et al , 2015), concentrating transcription factors in nucleoli (Berry et al , 2015), and the initiation of microtubule spindle formation…”
Competing protein-RNA interaction networks control multiphase intracellular organization (2020, neutral): “, NPM1, nucleolus) (Mitrea and Kriwacki, 2016), G3BP features a modular architecture with a”
Pi-Pi contacts are an overlooked protein feature relevant to phase separation (2018, background): “Thus, this represents a valuable tool for the currently expanding field of protein phase separation and its link to biological function and disease (Mitrea and Kriwacki, 2016; Conicella et al., 2016; Patel et al., 2015).”
ALS mutations disrupt phase separation mediated by -helical structure in the TDP-43 low complexity C-terminal domain (2016, background): “These domains can encode dynamic self-assembly into intracellular membraneless organelles or puncta including nucleoli and ribonucleoprotein (RNP) granules (Kato et al., 2012; Mitrea and Kriwacki, 2016; Nott et al., 2015).”
Intrinsically Disordered Proteins and Their “Mysterious” (Meta)Physics (2019, background): “Reversible Hydrogels In addition to liquid-liquid phase transitions, some proteins can (at least in vitro) undergo liquid-gel phase separation leading to the formation of hydrogels [211].”
Protein Phase Separation: A New Phase in Cell Biology (2018, background): “, stress granules (SGs), processing bodies, the centriole] [2,3].”