دورية أكاديمية
The proline-rich domain promotes Tau liquid-liquid phase separation in cells.
العنوان: | The proline-rich domain promotes Tau liquid-liquid phase separation in cells. |
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المؤلفون: | Zhang X; Department of Molecular, Cell and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA.; Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA., Vigers M; Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, CA.; Department of Chemical Engineering, University of California, Santa Barbara, Santa Barbara, CA., McCarty J; Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, CA., Rauch JN; Department of Molecular, Cell and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA.; Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA., Fredrickson GH; Department of Chemical Engineering, University of California, Santa Barbara, Santa Barbara, CA., Wilson MZ; Department of Molecular, Cell and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA.; Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA., Shea JE; Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, CA.; Department of Physics, University of California, Santa Barbara, Santa Barbara, CA., Han S; Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, CA.; Department of Chemical Engineering, University of California, Santa Barbara, Santa Barbara, CA., Kosik KS; Department of Molecular, Cell and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA.; Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA. |
المصدر: | The Journal of cell biology [J Cell Biol] 2020 Nov 02; Vol. 219 (11). |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
اللغة: | English |
بيانات الدورية: | Publisher: Rockefeller University Press Country of Publication: United States NLM ID: 0375356 Publication Model: Print Cited Medium: Internet ISSN: 1540-8140 (Electronic) Linking ISSN: 00219525 NLM ISO Abbreviation: J Cell Biol Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: New York : Rockefeller University Press |
مواضيع طبية MeSH: | Protein Aggregation, Pathological*, Liquid-Liquid Extraction/*methods , Neuroblastoma/*pathology , Proline/*chemistry , Proline/*metabolism , tau Proteins/*chemistry , tau Proteins/*metabolism, Cell Separation/methods ; Humans ; Microtubules ; Neuroblastoma/metabolism ; Phosphorylation ; Protein Binding ; Tumor Cells, Cultured |
مستخلص: | Tau protein in vitro can undergo liquid-liquid phase separation (LLPS); however, observations of this phase transition in living cells are limited. To investigate protein state transitions in living cells, we attached Cry2 to Tau and studied the contribution of each domain that drives the Tau cluster in living cells. Surprisingly, the proline-rich domain (PRD), not the microtubule binding domain (MTBD), drives LLPS and does so under the control of its phosphorylation state. Readily observable, PRD-derived cytoplasmic condensates underwent fusion and fluorescence recovery after photobleaching consistent with the PRD LLPS in vitro. Simulations demonstrated that the charge properties of the PRD predicted phase separation. Tau PRD formed heterotypic condensates with EB1, a regulator of plus-end microtubule dynamic instability. The specific domain properties of the MTBD and PRD serve distinct but mutually complementary roles that use LLPS in a cellular context to implement emergent functionalities that scale their relationship from binding α-beta tubulin heterodimers to the larger proportions of microtubules. (© 2020 Zhang et al.) |
References: | Cell. 2009 Jul 23;138(2):366-76. (PMID: 19632184) Science. 2018 May 25;360(6391):918-921. (PMID: 29650702) Nat Cell Biol. 2019 Sep;21(9):1078-1085. (PMID: 31481790) Nat Methods. 2013 Mar;10(3):249-52. (PMID: 23377377) Neuron. 2019 Apr 17;102(2):339-357.e7. (PMID: 30853299) Cytoskeleton (Hoboken). 2014 Sep;71(9):530-41. (PMID: 25160006) J Cell Biol. 2008 Dec 29;183(7):1223-33. (PMID: 19103809) Cell Rep. 2017 Sep 5;20(10):2304-2312. (PMID: 28877466) ACS Chem Neurosci. 2020 Feb 19;11(4):615-627. (PMID: 31971365) J Chem Phys. 2010 Jan 14;132(2):024104. (PMID: 20095660) Nature. 2020 May;581(7807):209-214. (PMID: 32405004) Cell. 2015 Aug 27;162(5):1066-77. (PMID: 26317470) Methods Mol Biol. 2013;1078:9-21. (PMID: 23975817) Mol Cell. 2015 Mar 5;57(5):936-947. (PMID: 25747659) Nature. 2017 Jul 13;547(7662):185-190. (PMID: 28678775) Nat Commun. 2019 May 1;10(1):2006. (PMID: 31043593) Proc Natl Acad Sci U S A. 2015 Jun 9;112(23):7189-94. (PMID: 26015579) J Biol Chem. 2019 Dec 13;294(50):19381-19394. (PMID: 31699899) Nat Methods. 2014 Jun;11(6):633-6. (PMID: 24793453) Nat Biotechnol. 2019 Dec;37(12):1435-1445. (PMID: 31792412) Neuron. 2019 Apr 17;102(2):321-338.e8. (PMID: 30826182) J Mol Biol. 2001 Nov 9;313(5):1045-57. (PMID: 11700061) EMBO J. 2018 Apr 3;37(7):. (PMID: 29472250) J Biol Chem. 2005 Jul 1;280(26):24978-86. (PMID: 15855160) PLoS Biol. 2017 Jul 6;15(7):e2002183. (PMID: 28683104) Ageing Res Rev. 2013 Jan;12(1):289-309. (PMID: 22742992) Proc Natl Acad Sci U S A. 2018 Dec 26;115(52):13234-13239. (PMID: 30538196) Nat Rev Neurosci. 2016 Jan;17(1):5-21. (PMID: 26631930) Cytoskeleton (Hoboken). 2010 Jan;67(1):1-12. (PMID: 19701929) Biochemistry. 1994 Aug 16;33(32):9511-22. (PMID: 8068626) Cell. 2017 Jan 12;168(1-2):159-171.e14. (PMID: 28041848) Curr Biol. 2010 Jun 22;20(12):R528-37. (PMID: 20620909) Mol Cell. 2015 Oct 15;60(2):208-19. (PMID: 26412307) Cell. 2019 Jan 24;176(3):419-434. (PMID: 30682370) Cell. 2015 Sep 24;163(1):123-33. (PMID: 26406374) Nat Commun. 2014 Sep 18;5:4925. (PMID: 25233328) J Cell Sci. 2010 Oct 15;123(Pt 20):3415-9. (PMID: 20930136) Science. 2018 Jun 15;360(6394):1242-1246. (PMID: 29748322) Nature. 2007 Dec 13;450(7172):1100-5. (PMID: 18059460) J Cell Sci. 2018 Oct 31;132(4):. (PMID: 30262468) Cell. 2015 Aug 13;162(4):849-59. (PMID: 26234155) Curr Biol. 2000 Jul 13;10(14):865-8. (PMID: 10899006) Mol Biol Cell. 2016 Oct 1;27(19):2924-34. (PMID: 27466319) J Cell Biol. 2009 Mar 9;184(5):691-706. (PMID: 19255245) Elife. 2019 Apr 05;8:. (PMID: 30950394) J Neural Transm (Vienna). 2005 Jun;112(6):813-38. (PMID: 15517432) Nat Cell Biol. 2008 Apr;10(4):415-21. (PMID: 18364701) Nat Cell Biol. 2019 Sep;21(9):1086-1092. (PMID: 31481789) Biomolecules. 2016 Jun 07;6(2):. (PMID: 27338491) Nat Commun. 2017 Aug 17;8(1):275. (PMID: 28819146) |
معلومات مُعتمدة: | K99 AG064116 United States AG NIA NIH HHS; R01 AG056058 United States AG NIA NIH HHS; U54 NS100717 United States NS NINDS NIH HHS |
المشرفين على المادة: | 0 (tau Proteins) 9DLQ4CIU6V (Proline) |
تواريخ الأحداث: | Date Created: 20200930 Date Completed: 20210330 Latest Revision: 20230413 |
رمز التحديث: | 20230413 |
مُعرف محوري في PubMed: | PMC7594490 |
DOI: | 10.1083/jcb.202006054 |
PMID: | 32997736 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1540-8140 |
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DOI: | 10.1083/jcb.202006054 |