Nature Reviews Chemistry, Journal Year: 2019, Volume and Issue: 3(9), P. 552 - 561
Published: July 25, 2019
Language: Английский
Cell, Journal Year: 2019, Volume and Issue: 176(3), P. 419 - 434
Published: Jan. 1, 2019
Language: Английский
Citations
2408
Annual Review of Biophysics, Journal Year: 2020, Volume and Issue: 49(1), P. 107 - 133
Published: Jan. 31, 2020
Many biomolecular condensates appear to form via spontaneous or driven processes that have the hallmarks of intracellular phase transitions. This suggests a common underlying physical framework might govern formation functionally and compositionally unrelated condensates. In this review, we summarize recent work leverages stickers-and-spacers adapted from field associative polymers for understanding how multivalent protein RNA molecules drive transitions give rise We discuss valence stickers impacts driving forces condensate elaborate on can be distinguished spacers in different contexts. touch impact sticker- spacer-mediated interactions rheological properties show model mapped known drivers types
Language: Английский
Citations
816
Nature Reviews Molecular Cell Biology, Journal Year: 2020, Volume and Issue: 22(3), P. 215 - 235
Published: Nov. 9, 2020
Language: Английский
Citations
693
Annual Review of Physical Chemistry, Journal Year: 2020, Volume and Issue: 71(1), P. 53 - 75
Published: April 20, 2020
Biological phase separation is known to be important for cellular organization, which has recently been extended a new class of biomolecules that form liquid-like droplets coexisting with the surrounding or extracellular environment. These are termed membraneless organelles, as they lack dividing lipid membrane, and formed through liquid-liquid (LLPS). Elucidating molecular determinants critical challenge field, we still at early stages understanding how cells may promote regulate functions driven by LLPS. In this review, discuss role disorder, perturbations interactions resulting from sequence, posttranslational modifications, various regulatory stimuli play on protein LLPS, particular focus insights obtained simulation theory. We finally these driving forces alter multicomponent selectivity.
Language: Английский
Citations
560
Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 23(5), P. 329 - 349
Published: Jan. 18, 2022
Language: Английский
Citations
541
Molecular Cell, Journal Year: 2019, Volume and Issue: 76(2), P. 286 - 294
Published: Oct. 1, 2019
Stress granules and P-bodies are cytosolic biomolecular condensates that dynamically form by the phase separation of RNAs proteins. They participate in translational control buffer proteome. Upon stress, global translation halts mRNAs bound to machinery other proteins coalesce stress (SGs). Similarly, translationally stalled devoid initiation factors shuttle (PBs). Here, we review cumulative progress made defining protein components associate with mammalian SGs PBs. We discuss composition SG PB proteomes, supported a new user-friendly database (http://rnagranuledb.lunenfeld.ca/) curates current literature evidence for genes or associated As previously observed, proteomes biased toward intrinsically disordered regions have high propensity contain primary sequence features favoring separation. also provide an outlook on how various PBs may cooperate organize membraneless organelles.
Language: Английский
Citations
369
Journal of Biological Chemistry, Journal Year: 2018, Volume and Issue: 294(18), P. 7137 - 7150
Published: Dec. 27, 2018
Language: Английский
Citations
339
Molecular Cell, Journal Year: 2019, Volume and Issue: 76(2), P. 295 - 305
Published: Oct. 1, 2019
Biomolecular condensation is emerging as an essential process for cellular compartmentalization. The formation of biomolecular condensates can be driven by liquid-liquid phase separation, which arises from weak, multivalent interactions among proteins and nucleic acids. A substantial body recent work has revealed that diverse processes rely on aberrant separation may cause disease. Many display intrinsic propensity to undergo separation. However, the mechanisms cells regulate build functional at appropriate time location are only beginning understood. Here, we review three key enable control separation: membrane surfaces, post-translational modifications, active processes. We discuss how these function in concert provide robust over suggest new research avenues will elucidate maintain centers compartmentalization into distinct, volumes life. All require partitioning molecules separate compartments carry out condensates, composed phase-separated protein acid, critical (Banani et al., 2017Banani S.F. Lee H.O. Hyman A.A. Rosen M.K. condensates: organizers biochemistry.Nat. Rev. Mol. Cell Biol. 2017; 18: 285-298Crossref PubMed Scopus (418) Google Scholar). These structures often behave liquid-like droplets, component mobile exchange with surrounding medium (Brangwynne 2015Brangwynne C. Tompa P. Pappu R. Polymer physics intracellular transitions.Nat. Phys. 2015; 11: 899-904Crossref (228) In this review, refer entities or networks, clusters. Phase-separated found physiological contexts throughout cell, including nucleoli 2011Brangwynne C.P. Mitchison T.J. Active behavior determines their size shape Xenopus laevis oocytes.Proc. Natl. Acad. Sci. USA. 2011; 108: 4334-4339Crossref (298) Scholar) P granules 2009Brangwynne Eckmann C.R. Courson D.S. Rybarska A. Hoege Gharakhani J. Jülicher F. Germline liquid droplets localize controlled dissolution/condensation.Science. 2009; 324: 1729-1732Crossref (611) Scholar), unique biophysical identities (Langdon 2018Langdon E.M. Qiu Y. Ghanbari Niaki McLaughlin G.A. Weidmann C.A. Gerbich T.M. Smith J.A. Crutchley J.M. Termini C.M. Weeks K.M. al.mRNA structure specificity a polyQ-driven separation.Science. 2018; 360: 922-927Crossref (1) Scholar, Zhang 2015Zhang H. Elbaum-Garfinkle S. Langdon Taylor N. Occhipinti Bridges Brangwynne Gladfelter A.S. RNA Controls PolyQ Protein Phase Transitions.Mol. Cell. 60: 220-230Abstract Full Text PDF (184) addition roles cell physiology, involved pathological aggregates neurodegenerative diseases such amyotrophic lateral sclerosis (ALS) (Patel 2015Patel Jawerth L. Maharana Jahnel M. Hein M.Y. Stoynov Mahamid Saha Franzmann al.A Liquid-to-Solid Transition ALS FUS Accelerated Disease Mutation.Cell. 162: 1066-1077Abstract (509) feature many proteins; form spontaneously sufficient concentration vitro when overexpressed (Shin Brangwynne, 2017Shin Liquid physiology disease.Science. 357: eaaf4382Crossref (247) must natural tendency acids correct location. thus part understanding use (Alberti 2019Alberti Mittag T. Considerations Challenges Studying Liquid-Liquid Separation Condensates.Cell. 2019; 176: 419-434Abstract (0) between acids, collectively facilitate condensed network other related material properties (Pak 2016Pak C.W. Kosno Holehouse Padrick S.B. Mittal Ali Yunus Liu D.R. R.V. Sequence Determinants Intracellular Complex Coacervation Disordered Protein.Mol. 2016; 63: 72-85Abstract Shin variety different types electrostatic, cation-π, π-π, dipole-dipole (Banjade 2015Banjade Wu Q. Peeples W.B. Conserved interdomain linker promotes adaptor Nck.Proc. 112: E6426-E6435Crossref (27) Das Pappu, 2013Das R.K. Conformations intrinsically disordered influenced linear sequence distributions oppositely charged residues.Proc. 2013; 110: 13392-13397Crossref (233) Nott 2015Nott Petsalaki E. Farber Jervis D. Fussner Plochowietz Craggs T.D. Bazett-Jones D.P. Pawson Forman-Kay J.D. Baldwin A.J. transition nuage generates environmentally responsive membraneless organelles.Mol. 57: 936-947Abstract (334) Vernon 2018Vernon R.M. Chong P.A. Tsang B. Kim T.H. Bah Lin Pi-Pi contacts overlooked relevant separation.eLife. 7: e31486Crossref Wang 2018bWang Choi X. Lemaitre Pozniakovsky Drechsel Molecular Grammar Governing Driving Forces Prion-like Binding Proteins.Cell. 174: 688-699.e16Abstract How do separation? More broadly, what governing parameters manipulate defined identities? Some include concentrations molecular components, valencies strengths interaction molecules, initial nucleation seeding event, environmental ionic strength pH, thermodynamic temperature. By toggling where assemble, rates assembly disassembly, viscosity surface tension. While have limited parameters, several regulatory For example, surfaces regulation required well event (Figure 1). Specifically, restrict diffusion two-dimensional plane, lowering threshold providing timing nucleation. another important modifications (PTMs) valency protein-protein Finally, chaperones modify restructure architecture emergent transform "active matter" readily adapt environments potentially states. advances our PTMs, regulating transitions. process, highlight areas lacking, future directions space. Membrane platforms condensates. two dimensions, reducing 2A). ability concentrate long been recognized context signaling cascades, enhance increasing local compared cytosol (Kholodenko 2000Kholodenko B.N. Hoek J.B. Westerhoff H.V. Why cytoplasmic signalling should recruited membranes.Trends 2000; 10: 173-178Abstract (147) fact, assemble macroscopic clusters membranes upon activation extracellular cue, facilitating amplified individual proteins. Although studied extensively pathways, it recently becoming appreciated hallmarks systems Rosen, 2014Banjade transitions promote clustering receptors.eLife. 2014; 3: e04123Crossref Case 2019aCase L.B. Ditlev Regulation Transmembrane Signaling Separation.Annu. Biophys. 48: 465-494Crossref Huang 2016Huang W.Y. Yan W.C. Chung J.K. Hansen S.D. Christensen S.M. Tu H.L. Kuriyan Groves J.T. Phosphotyrosine-mediated LAT drives kinetic bifurcation recruitment dynamics Ras activator SOS.Proc. 113: 8218-8223Crossref (22) Su 2016Su Hui Xing W. Banjade Okrut King Taunton Vale R.D. T receptor signal transduction.Science. 352: 595-599Crossref (363) example transmembrane (LAT). becomes phosphorylated receptor, membrane-bound Grb2 Son Sevenless (SOS) (Houtman 2006Houtman J.C.D. Yamaguchi Barda-Saad Braiman Bowden Appella Schuck Samelson L.E. Oligomerization complexes multipoint binding GRB2 both SOS1.Nat. Struct. 2006; 13: 798-805Crossref (128) SH2 domain binds phosphotyrosines LAT, while SH3 domains bind proline-rich SOS. Once bound membrane, SOS undergoes conformational change facilitates propagation downstream signals (Iversen 2014Iversen Abel Iwig H.J. Gureasko Rhodes Petit R.S. al.Molecular kinetics. SOS: allosteric altered fluctuation dynamics.Science. 345: 50-54Crossref (61) Recent separates supported lipid bilayers macroscopic, (Huang 2017Su Reconstitution TCR Using Supported Lipid Bilayers.Methods 1584: 65-76Crossref (4) consistent predictions earlier theoretical (Nag 2009Nag Monine M.I. Faeder J.R. Goldstein Aggregation cytosolic cross-linkers: theory simulation LAT-Grb2-SOS1 system.Biophys. 96: 2604-2623Abstract (46) were increase dwell SOS, probability undergoing changes necessary Membrane-bound thereby distinguish transient true signals. study provided more in-depth examination "kinetic proofreading" mechanism 2019Huang W.Y.C. Alvarez Kondo Y.K. Lam H.Y.M. Biswas K.H. proofreading modulate SOS.Science. 363: 1098-1103Crossref (8) Moreover, recruit kinases exclude phosphatases, promoting toward actin polymerization (Su particular, promoted Nck N-WASP Arp2/3 membrane. Thus, localized response specific stimuli. demonstrated contexts. nephrin-Nck-N-WASP system, regulates kidney podocyte (Jones 2006Jones Blasutig I.M. Eremina V. Ruston Bladt Li Larose S.S.C. Takano al.Nck link nephrin cytoskeleton podocytes.Nature. 440: 818-823Crossref (325) also Nephrin tail containing phosphotyrosines. interact nephrin, N-WASP. Collectively, multivalent, (Li 2012Li Cheng H.C. Chen Guo Llaguno Hollingsworth J.V. Banani al.Phase proteins.Nature. 2012; 483: 336-340Crossref (539) capable driving Lower observe comparison formed solution This finding supports role increases filament nucleator leading increased site (Case 2019bCase Stoichiometry controls activity proteins.Science. 1093-1097Crossref stoichiometry components within was influence times Arp2/3, fine tuning locally functions context-dependent manner. studies demonstrate assembling polymerization. nephrin- LAT-based networks best-characterized examples act general platform notable shown organization synaptic vesicles (Milovanovic 2018Milovanovic Bian De Camilli synapsin vesicles.Science. 361: 604-607Crossref (3) condensate capturing accumulating nerve terminals. report, presynaptic before transmission (Wu 2019Wu Cai Shen Z. Zeng Du RIM RIM-BP Form Presynaptic Active-Zone-like Condensates via Separation.Mol. 73: 971-984.e5Abstract (2) work, scaffold RIM-BP, voltage-gated calcium channels zone neurons (Südhof, 2012Südhof T.C. zone.Neuron. 75: 11-25Abstract (389) bilayers, forming two-dimensional, enriched channels, supporting helping organize membranes. suggests serves organizing zones. Studies primarily focused plasma endomembrane cell. showed RNA-binding TIS11B meshwork intertwined endoplasmic reticulum (ER) (Ma Mayr, 2018Ma Mayr Membraneless Organelle Associated Endoplasmic Reticulum Enables 3'UTR-Mediated Protein-Protein Interactions.Cell. 175: 1492-1506.e19Abstract complex forms distinct subcellular compartment trafficking surface. influenza viral ribonucleoprotein particles, qualities ER exit sites (Alenquer 2019Alenquer Vale-Costa Etibor T.A. Ferreira Sousa A.L. Amorim M.J. Influenza virus ribonucleoproteins organelles sites.Nat. Commun. 1629Crossref reports serve occupies fraction volume rapidly explores cytoplasm (Nixon-Abell 2016Nixon-Abell Obara C.J. Weigel A.V. Legant W.R. Xu C.S. Pasolli H.A. Harvey K. Hess H.F. Betzig al.Increased spatiotemporal resolution reveals highly dynamic dense tubular matrices peripheral ER.Science. 354: 12Crossref (100) Valm 2017Valm A.M. Cohen Melunis Hershberg U. Wait A.R. Davidson M.W. Lippincott-Schwartz Applying systems-level spectral imaging analysis reveal organelle interactome.Nature. 546: 162-167Crossref (117) suggesting regulator One could space contacting communicating 2B). signaling, materials, biogenesis (Fernández-Busnadiego 2015Fernández-Busnadiego Saheki Three-dimensional extended synaptotagmin-mediated reticulum-plasma contact sites.Proc. E2004-E2013Crossref Phillips Voeltz, 2016Phillips Voeltz G.K. Structure organelles.Nat. 17: 69-82Crossref (253) apposed not directly touch fuse, assemblies interfaces tethering (Phillips An interesting hypothesis organelles. Future spatially patterned temporally interfaces. It likely transfer materials organizes interface ER-Golgi intermediate early secretory pathway (Hanna 2017Hanna 4th, M.G. Block Frankel E.B. Hou Johnson Yuan Knight G. Moresco J.J. Yates 3rd, Ashton al.TFG outer coat disassembly COPII transport carriers fusion compartments.Proc. 114: E7707-E7716Crossref (5) 2015Johnson Bhattacharya Hanna Pennington J.G. Schuh Otegui M.S. Stagg Audhya TFG COPII-coated organization.EMBO 34: 811-827Crossref coated compartment. authors hypothesize efficiently concentrates vesicles, ensuring efficient secretion preventing dispersal away findings stabilize sites, although needed examine play positioning cells. Previous co-transported endosomes along microtubules, some RNA-based docking endosomal shuttled distances (Baumann 2012Baumann Pohlmann Jungbluth Brachmann Feldbrügge Kinesin-3 dynein mediate microtubule-dependent co-transport mRNPs endosomes.J. 125: 2740-2752Crossref transported lysosomes (Liao 2019Liao Y.C. Fernandopulle Hao Drerup Qamar Nixon-Abell Meadows al.RNA Granules Hitchhike Lysosomes Long-Distance Transport, Annexin A11 Tether.Cell. (Published online January 11, 2019)https://doi.org/10.2139/ssrn.3312723Crossref annexin acts tether attaches lysosomal granule hitchhiking microtubules. various condens
Language: Английский
Citations
313
Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)
Published: Sept. 15, 2020
Liquid phase separation into two or more coexisting phases has emerged as a new paradigm for understanding subcellular organization, prebiotic life, and the origins of disease. The design principles underlying biomolecular have potential to drive development novel liquid-based organelles therapeutics, however, an how individual molecules contribute emergent material properties, approaches directly manipulate dynamics are lacking. Here, using microrheology, we demonstrate that droplets poly-arginine coassembled with mono/polynucleotides approximately 100 fold greater viscosity than comparable lysine droplets, both which can be finer tuned by polymer length. We find these amino acid-level differences formation immiscible tunable kinetics further exploited trigger controlled release droplet components. Together, this work provides mechanism leveraging sequence-level components in order regulate multiphase coexistence.
Language: Английский
Citations
251
Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)
Published: July 2, 2019
Abstract Cells form and use biomolecular condensates to execute biochemical reactions. The molecular properties of non-membrane-bound are directly connected the amino acid content disordered protein regions. Lysine plays an important role in cellular function, but little is known about its condensation. Here we show that disorder abundant protein/RNA granules lysine enriched regions proteins P-bodies compared entire human proteome. Lysine-rich polypeptides phase separate into lysine/RNA-coacervates more dynamic differ at level from arginine/RNA-coacervates. Consistent with ability drive separation, lysine-rich variants Alzheimer’s disease-linked tau undergo coacervation RNA vitro bind stress cells. Acetylation reverses liquid–liquid separation reduces colocalization granules. Our study establishes as regulator
Language: Английский
Citations
222