エンジニアが初の試み:細胞凝縮液のpH測定(WashU engineers manage a first: measuring pH in cell condensates)

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2024-03-18 ワシントン大学セントルイス校

核小体の研究において、ワシントン大学のRohit Pappu教授らのチームが、核小体の独自のpHプロファイルを測定し、他の凝集体と比較した。核小体はリボソームの生産場所であり、リボソームの機能不全はがんや神経変性疾患などの病気の原因である。彼らの研究では、核小体の酸性特性が明らかにされ、これによって生物化学的な特異性が提唱される可能性があることが示唆された。

<関連情報>

高分子凝縮体が核小体を組織化してpH勾配を形成する Macromolecular condensation organizes nucleolar sub-phases to set up a pH gradient

Matthew R. King,Kiersten M. Ruff,Andrew Z. Lin,…,Emma Lundberg,Michael D. Vahey,Rohit V. Pappu
Cell  Published:March 18, 2024
DOI:https://doi.org/10.1016/j.cell.2024.02.029

Highlights

•Nucleolar IDRs are enriched in D/E tracts and K-blocks interspersed by E-rich regions

•Specificity of complex coacervation and hydrophobicity organize nucleolar layers

•Binding of protons to D/E tracts sets up pH gradients between nucleoli and nucleoplasm

•Condensate-specific pH values in the nucleus correlate with mean net charge of IDRs

Summary

Nucleoli are multicomponent condensates defined by coexisting sub-phases. We identified distinct intrinsically disordered regions (IDRs), including acidic (D/E) tracts and K-blocks interspersed by E-rich regions, as defining features of nucleolar proteins. We show that the localization preferences of nucleolar proteins are determined by their IDRs and the types of RNA or DNA binding domains they encompass. In vitro reconstitutions and studies in cells showed how condensation, which combines binding and complex coacervation of nucleolar components, contributes to nucleolar organization. D/E tracts of nucleolar proteins contribute to lowering the pH of co-condensates formed with nucleolar RNAs in vitro. In cells, this sets up a pH gradient between nucleoli and the nucleoplasm. By contrast, juxta-nucleolar bodies, which have different macromolecular compositions, featuring protein IDRs with very different charge profiles, have pH values that are equivalent to or higher than the nucleoplasm. Our findings show that distinct compositional specificities generate distinct physicochemical properties for condensates.

Graphical abstract

エンジニアが初の試み:細胞凝縮液のpH測定(WashU engineers manage a first: measuring pH in cell condensates)

 

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