Basal condensation of Numb and Pon complex via phase transition during Drosophila neuroblast asymmetric division

Nature Communications
Zelin ShanWenyu Wen

Abstract

Uneven distribution and local concentration of protein complexes on distinct membrane cortices is a fundamental property in numerous biological processes, including Drosophila neuroblast (NB) asymmetric cell divisions and cell polarity in general. In NBs, the cell fate determinant Numb forms a basal crescent together with Pon and is segregated into the basal daughter cell to initiate its differentiation. Here we discover that Numb PTB domain, using two distinct binding surfaces, recognizes repeating motifs within Pon in a previously unrecognized mode. The multivalent Numb-Pon interaction leads to high binding specificity and liquid-liquid phase separation of the complex. Perturbations of the Numb/Pon complex phase transition impair the basal localization of Numb and its subsequent suppression of Notch signaling during NB asymmetric divisions. Such phase-transition-mediated protein condensations on distinct membrane cortices may be a general mechanism for various cell polarity regulatory complexes.

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Citations

Nov 24, 2018·Biological Reviews of the Cambridge Philosophical Society·Ananya Barui, Pallab Datta
Oct 30, 2018·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Aleksej Drino, Matthias R Schaefer
Sep 13, 2019·Biomolecules·Boris Y ZaslavskyVladimir N Uversky
Feb 1, 2020·Annual Review of Biophysics·Jeong-Mo ChoiRohit V Pappu
Aug 25, 2020·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Alicia G GubiedaJosana Rodriguez
Sep 15, 2018·The Journal of Biological Chemistry·Weiyi YaoWenyu Wen
Jun 18, 2020·Science China. Life Sciences·Hong ZhangXueliang Zhu
May 10, 2020·Nature Communications·Ziheng LiuWenyu Wen
Jan 19, 2021·Current Opinion in Cell Biology·Khuloud Jaqaman, Jonathon A Ditlev
Feb 1, 2021·Briefings in Bioinformatics·Rita PancsaBálint Mészáros
Feb 21, 2019·Developmental Cell·Kristina N Schaefer, Mark Peifer
Aug 3, 2021·Signal Transduction and Targeted Therapy·Bin WangFangfang Zhou
Aug 12, 2021·Biochemistry·Heyang Wei, Wenyu Wen
Apr 29, 2020·Biomacromolecules·Miao LiuJiang Xia
Oct 17, 2019·Biochemistry·Wenyu Wen
Jul 30, 2020·Developmental Cell·Xiandeng WuMingjie Zhang

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Methods Mentioned

BETA
pull-down
fluorescence microscopy
transgenic
size-exclusion chromatography
electrophoresis
transfection
transfections
Confocal microscopy

Software Mentioned

phenix
Adobe Illustrator
Origin
Leica Confocal SP8
COOT
Adobe Photoshop
PHASER

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