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
-
- Zebrafish
- Basal Bodies/physiology*
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/metabolism
- Signal Transduction/genetics
- Receptors, Notch/metabolism*
- Mutation/genetics
- Microtubule-Associated Proteins/genetics
- Microtubule-Associated Proteins/metabolism*
- Transcription Factors/genetics
- Transcription Factors/metabolism
- Humans
- Drosophila
- Cilia/physiology*
- Animals
- Cell Line
- Endosomal Sorting Complexes Required for Transport/genetics
- Endosomal Sorting Complexes Required for Transport/metabolism
- Endosomes/metabolism*
- Cell Membrane/metabolism*
- Proteins/genetics
- Proteins/metabolism*
- Protein Transport/genetics
- ADP-Ribosylation Factors/genetics
- ADP-Ribosylation Factors/metabolism
- PubMed
- 24681783 Full text @ J. Cell Sci.
Citation
Leitch, C.C., Lodh, S., Prieto-Echagüe, V., Badano, J.L., Zaghloul, N.A. (2014) Basal body proteins regulate Notch signaling via endosomal trafficking. Journal of Cell Science. 127(Pt 11):2407-19.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping