PUBLICATION

PCM1 coordinates centrosome asymmetry with polarized endosome dynamics to regulate daughter cell fate

Authors
Zhao, X., Mouilleau, V., Wang, Y., Solak, A.C., Garcia, J.Q., Chen, X., Shi, X., Wilkinson, C.J., Royer, L.A., Dong, Z., Guo, S.
ID
ZDB-PUB-251129-12
Date
2025
Source
Nature communications   16: 1072810728 (Journal)
Registered Authors
Dong, Zhiqiang, Guo, Su
Keywords
none
MeSH Terms
  • Animals
  • Asymmetric Cell Division
  • Cell Cycle Proteins*/genetics
  • Cell Cycle Proteins*/metabolism
  • Cell Differentiation
  • Cell Polarity
  • Centrosome*/metabolism
  • Dyneins/metabolism
  • Endosomes*/metabolism
  • Humans
  • Neural Stem Cells/cytology
  • Neural Stem Cells/metabolism
  • Zebrafish/embryology
  • Zebrafish/metabolism
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
  • rab GTP-Binding Proteins/metabolism
  • rab5 GTP-Binding Proteins/metabolism
PubMed
41315244 Full text @ Nat. Commun.
Abstract
Vertebrate radial glia progenitors (RGPs) balance self-renewal and differentiation through asymmetric cell division (ACD), which involves unequal centrosome inheritance. How centrosome asymmetry directs cell fate remains poorly understood. Here, we identify Pericentriolar material 1 (Pcm1) as a key player in this process. In zebrafish embryonic RGPs, Pcm1 is asymmetrically associated with Cep83, a mother centrosome marker. Using in vivo time-lapse imaging and nanoscale-resolution expansion microscopy, we detect Pcm1 on Notch ligand-containing endosomes, where it interacts-either directly or indirectly-with Par-3 and dynein. Loss of pcm1 disrupts endosome dynamics, increasing neuronal differentiation at the expense of RGP self-renewal. Mechanistically, Pcm1 facilitates the transition from Rab5b to Rab11a and promotes the assembly of Par-3 and dynein macromolecular complexes on recycling endosomes. Furthermore, we find conserved PARD3-PCM1-CEP83-RAB11 associations in human cortical brain organoids. Our findings uncover that Pcm1 links centrosome asymmetry to polarized endosome trafficking, thereby regulating RGP fate decisions.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping