Assemblages: Functional Units Formed by Cellular Phase Separation

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2014 Sep 3

PMID 25179628

Citations 127

Authors

Jeffrey A Toretsky

Peter E Wright

Affiliations

Soon will be listed here.

Abstract

The partitioning of intracellular space beyond membrane-bound organelles can be achieved with collections of proteins that are multivalent or contain low-complexity, intrinsically disordered regions. These proteins can undergo a physical phase change to form functional granules or other entities within the cytoplasm or nucleoplasm that collectively we term "assemblage." Intrinsically disordered proteins (IDPs) play an important role in forming a subset of cellular assemblages by promoting phase separation. Recent work points to an involvement of assemblages in disease states, indicating that intrinsic disorder and phase transitions should be considered in the development of therapeutics.

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References

Delattre O, ZUCMAN J, Plougastel B, Desmaze C, Melot T, Peter M . Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature. 1992; 359(6391):162-5. DOI: 10.1038/359162a0. View

Weber S, Brangwynne C . Getting RNA and protein in phase. Cell. 2012; 149(6):1188-91. DOI: 10.1016/j.cell.2012.05.022. View

Mittag T, Orlicky S, Choy W, Tang X, Lin H, Sicheri F . Dynamic equilibrium engagement of a polyvalent ligand with a single-site receptor. Proc Natl Acad Sci U S A. 2008; 105(46):17772-7. PMC: 2582940. DOI: 10.1073/pnas.0809222105. View

Li P, Banjade S, Cheng H, Kim S, Chen B, Guo L . Phase transitions in the assembly of multivalent signalling proteins. Nature. 2012; 483(7389):336-40. PMC: 3343696. DOI: 10.1038/nature10879. View

Adams R, Wente S . Uncovering nuclear pore complexity with innovation. Cell. 2013; 152(6):1218-21. PMC: 3672239. DOI: 10.1016/j.cell.2013.02.042. View

Wimmer C, Doye V, Grandi P, Nehrbass U, Hurt E . A new subclass of nucleoporins that functionally interact with nuclear pore protein NSP1. EMBO J. 1992; 11(13):5051-61. PMC: 556983. DOI: 10.1002/j.1460-2075.1992.tb05612.x. View

Tompa P . Hydrogel formation by multivalent IDPs: A reincarnation of the microtrabecular lattice?. Intrinsically Disord Proteins. 2017; 1(1):e24068. PMC: 5424804. DOI: 10.4161/idp.24068. View

King O, Gitler A, Shorter J . The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease. Brain Res. 2012; 1462:61-80. PMC: 3372647. DOI: 10.1016/j.brainres.2012.01.016. View

Gitler A, Shorter J . RNA-binding proteins with prion-like domains in ALS and FTLD-U. Prion. 2011; 5(3):179-87. PMC: 3226045. DOI: 10.4161/pri.5.3.17230. View

10.

Uren A, Toretsky J . Ewing's sarcoma oncoprotein EWS-FLI1: the perfect target without a therapeutic agent. Future Oncol. 2006; 1(4):521-8. DOI: 10.2217/14796694.1.4.521. View

11.

Updike D, Hachey S, Kreher J, Strome S . P granules extend the nuclear pore complex environment in the C. elegans germ line. J Cell Biol. 2011; 192(6):939-48. PMC: 3063144. DOI: 10.1083/jcb.201010104. View

12.

Gao M, Arkov A . Next generation organelles: structure and role of germ granules in the germline. Mol Reprod Dev. 2012; 80(8):610-23. PMC: 3584238. DOI: 10.1002/mrd.22115. View

13.

Pentony M, Jones D . Modularity of intrinsic disorder in the human proteome. Proteins. 2009; 78(1):212-21. DOI: 10.1002/prot.22504. View

14.

Caron N, Desmond C, Xia J, Truant R . Polyglutamine domain flexibility mediates the proximity between flanking sequences in huntingtin. Proc Natl Acad Sci U S A. 2013; 110(36):14610-5. PMC: 3767516. DOI: 10.1073/pnas.1301342110. View

15.

Labbadia J, Morimoto R . Huntington's disease: underlying molecular mechanisms and emerging concepts. Trends Biochem Sci. 2013; 38(8):378-85. PMC: 3955166. DOI: 10.1016/j.tibs.2013.05.003. View

16.

Marlow F, Mullins M . Bucky ball functions in Balbiani body assembly and animal-vegetal polarity in the oocyte and follicle cell layer in zebrafish. Dev Biol. 2008; 321(1):40-50. PMC: 2606906. DOI: 10.1016/j.ydbio.2008.05.557. View

17.

Huang B, Babcock H, Zhuang X . Breaking the diffraction barrier: super-resolution imaging of cells. Cell. 2010; 143(7):1047-58. PMC: 3272504. DOI: 10.1016/j.cell.2010.12.002. View

18.

Mao A, Crick S, Vitalis A, Chicoine C, Pappu R . Net charge per residue modulates conformational ensembles of intrinsically disordered proteins. Proc Natl Acad Sci U S A. 2010; 107(18):8183-8. PMC: 2889596. DOI: 10.1073/pnas.0911107107. View

19.

Li Y, King O, Shorter J, Gitler A . Stress granules as crucibles of ALS pathogenesis. J Cell Biol. 2013; 201(3):361-72. PMC: 3639398. DOI: 10.1083/jcb.201302044. View

20.

Vavouri T, Semple J, Garcia-Verdugo R, Lehner B . Intrinsic protein disorder and interaction promiscuity are widely associated with dosage sensitivity. Cell. 2009; 138(1):198-208. DOI: 10.1016/j.cell.2009.04.029. View