Basal condensation of Numb and Pon complex via
phase transition during Drosophila neuroblast
, Yuting Tu
, Ying Yang
, Ziheng Liu
, Menglong Zeng
, Huisha Xu
, Jiafu Long
, Yu Cai
& Wenyu Wen
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.
Department of Neurosurgery, Huashan Hospital, Institutes of Biomedical Sciences, State Key Laboratory of Medical Neurobiology, Department of Systems
Biology for Medicine, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China.
Temasek Life Sciences
Laboratory, Department of Biological Sciences, National University of Singapore, Singapore 117604, Singapore.
Division of Life Science, State Key Laboratory
of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
State Key Laboratory of
Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China. Zelin Shan, Yuting Tu and Ying Yang contributed equally to
this work. Correspondence and requests for materials should be addressed to Y.C. (email: firstname.lastname@example.org) or to W.W. (email: email@example.com)