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. |
|---|---|
| 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.) |
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| 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 |
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