The proline-rich domain promotes Tau liquid-liquid phase separation in cells

Xuemei Zhang, Michael Vigers, James McCarty, Jennifer N. Rauch, Glenn H. Fredrickson, Maxwell Z. Wilson, Joan Emma Shea, Songi Han, Kenneth S. Kosik*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

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, PRDderived 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.

Original languageEnglish (US)
Article numbere202006054
JournalJournal of Cell Biology
Volume219
Issue number11
DOIs
StatePublished - 2020

ASJC Scopus subject areas

  • Cell Biology

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