PUBLICATION

Basal body proteins regulate Notch signaling via endosomal trafficking

Authors
Leitch, C.C., Lodh, S., Prieto-Echagüe, V., Badano, J.L., Zaghloul, N.A.
ID
ZDB-PUB-140513-249
Date
2014
Source
Journal of Cell Science   127(Pt 11): 2407-19 (Journal)
Registered Authors
Zaghloul, Norann A.
Keywords
none
MeSH Terms
  • Cell Line
  • Endosomal Sorting Complexes Required for Transport/genetics
  • Endosomal Sorting Complexes Required for Transport/metabolism
  • Signal Transduction/genetics
  • Protein Transport/genetics
  • Microtubule-Associated Proteins/genetics
  • Microtubule-Associated Proteins/metabolism*
  • Proteins/genetics
  • Proteins/metabolism*
  • Humans
  • Endosomes/metabolism*
  • Animals
  • Cell Membrane/metabolism*
  • Basal Bodies/physiology*
  • Receptors, Notch/metabolism*
  • Drosophila
  • Transcription Factors/genetics
  • Transcription Factors/metabolism
  • ADP-Ribosylation Factors/genetics
  • ADP-Ribosylation Factors/metabolism
  • Cilia/physiology*
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism
  • Mutation/genetics
  • Zebrafish
PubMed
24681783 Full text @ J. Cell Sci.
Abstract
Proteins associated with primary cilia and basal bodies mediate numerous signaling pathways, but little is known about their role in Notch signaling. Here we report that loss of Bardet-Biedl syndrome proteins, BBS1 or BBS4, produced increased Notch-directed transcription in a zebrafish reporter line and in human cell lines. Pathway overactivation was accompanied by reduced localization of Notch receptor at both the plasma membrane and the cilium. In Drosophila mutants, overactivation of Notch can result from receptor accumulation in endosomes and recent studies implicate ciliary proteins in endosomal trafficking, suggesting a possible mechanism by which overactivation occurs in BBS mutants. Consistent with this, we observed genetic interaction of BBS1/4 with the ESCRT gene TSG101 and accumulation of receptor in late endosomes, reduced endosomal recycling and reduced receptor degradation in lysosomes. We observed similar defects with disruption of BBS3. Loss of another basal body protein, ALMS1, also enhanced Notch activation and accumulation of receptor in late endosomes, but did not disrupt recycling. These findings suggest a role for these proteins in regulation of Notch via endosomal trafficking of the receptor.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping