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

Zelin Shan, Yuting Tu, Ying Yang, Ziheng Liu, Menglong Zeng, Huisha Xu, Jiafu Long, Mingjie Zhang, Yu Cai () and Wenyu Wen ()
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Zelin Shan: Shanghai Medical College of Fudan University
Yuting Tu: Shanghai Medical College of Fudan University
Ying Yang: National University of Singapore
Ziheng Liu: Shanghai Medical College of Fudan University
Menglong Zeng: Hong Kong University of Science and Technology
Huisha Xu: Nankai University
Jiafu Long: Nankai University
Mingjie Zhang: Hong Kong University of Science and Technology
Yu Cai: National University of Singapore
Wenyu Wen: Shanghai Medical College of Fudan University

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03077-3

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