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PMID: 29973724 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Kinase-controlled phase transition of membraneless organelles in mitosis.

Nature ·Vol. 559 ·No. 7713 ·2018-00-00 ·Pages 211-216

Rai AK, Chen JX, Selbach M, Pelkmans L

Abstract

Liquid-liquid phase separation has been shown to underlie the formation and disassembly of membraneless organelles in cells, but the cellular mechanisms that control this phenomenon are poorly understood. A prominent example of regulated and reversible segregation of liquid phases may occur during mitosis, when membraneless organelles disappear upon nuclear-envelope breakdown and reappear as mitosis is completed. Here we show that the dual-specificity kinase DYRK3 acts as a central dissolvase of several types of membraneless organelle during mitosis. DYRK3 kinase activity is essential to prevent the unmixing of the mitotic cytoplasm into aberrant liquid-like hybrid organelles and the over-nucleation of spindle bodies. Our work supports a mechanism in which the dilution of phase-separating proteins during nuclear-envelope breakdown and the DYRK3-dependent degree of their solubility combine to allow cells to dissolve and condense several membraneless organelles during mitosis.

MeSH Terms
Anaphase-Promoting Complex-Cyclosome/metabolism Cytoplasm/metabolism Cytoplasmic Granules/metabolism HEK293 Cells HeLa Cells Humans Mitosis Nuclear Envelope/metabolism Organelles/metabolism Poly(A)-Binding Protein I/metabolism Protein Binding Protein Serine-Threonine Kinases/antagonists & inhibitors,biosynthesis,metabolism Protein Transport Protein-Tyrosine Kinases/antagonists & inhibitors,biosynthesis,metabolism Solubility Spindle Apparatus/metabolism Stress, Physiological
Chemicals
Poly(A)-Binding Protein I Anaphase-Promoting Complex-Cyclosome DYRK3 protein, human Protein-Tyrosine Kinases Protein Serine-Threonine Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Rai Arpan Kumar
Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
Chen Jia-Xuan
Max Delbrück Center for Molecular Medicine, Berlin, Germany. | Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Selbach Matthias
Max Delbrück Center for Molecular Medicine, Berlin, Germany. | Charité-Universitätsmedizin Berlin, Berlin, Germany.
Pelkmans Lucas
Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland. lucas.pelkmans@imls.uzh.ch.
Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
Published
2018-00-00
Epub
2018-00-04
Pages
211-216
Language
English
Region
England
NLM ID
0410462
Subset
IM
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