PUBLICATION
The Rab11 effectors Fip5 and Fip1 regulate zebrafish intestinal development
- Authors
- Jewett, C.E., Appel, B.H., Prekeris, R.
- ID
- ZDB-PUB-201002-158
- Date
- 2020
- Source
- Biology Open 9(10): (Journal)
- Registered Authors
- Appel, Bruce
- Keywords
- FIP1, FIP5, Microvilli, RCP, Rab11, Rip11
- MeSH Terms
-
- Animals
- Carrier Proteins/genetics
- Carrier Proteins/metabolism*
- Endosomes
- Intestines/embryology*
- Microvilli/genetics
- Microvilli/metabolism
- Microvilli/ultrastructure
- Mutation
- Organogenesis/genetics*
- Phenotype
- Protein Binding
- Zebrafish/embryology*
- Zebrafish/genetics*
- rab GTP-Binding Proteins/metabolism*
- PubMed
- 32973079 Full text @ Biol. Open
Citation
Jewett, C.E., Appel, B.H., Prekeris, R. (2020) The Rab11 effectors Fip5 and Fip1 regulate zebrafish intestinal development. Biology Open. 9(10):.
Abstract
The Rab11 apical recycling endosome pathway is a well-established regulator of polarity and lumen formation; however, Rab11-vesicular trafficking also directs a diverse array of other cellular processes, raising the question of how Rab11 vesicles achieve specificity in space, time, and content of cargo delivery. In part, this specificity is achieved through effector proteins, yet the role of Rab11 effector proteins in vivo remains vague. Here, we use CRISPR/Cas9 gene editing to study the role of the Rab11 effector Fip5 during zebrafish intestinal development. Zebrafish contain two paralogous genes, fip5a and fip5b, that are orthologs of human FIP5 We find that fip5a and fip5b mutant fish show phenotypes characteristic of microvillus inclusion disease, including microvilli defects and lysosomal accumulation. Single and double mutant analyses suggest that fip5a and fip5b function in parallel and regulate trafficking pathways required for assembly of keratin at the terminal web. Remarkably, in some genetic backgrounds, the absence of Fip5 triggers protein upregulation of a closely related family member, Fip1. This compensation mechanism occurs both during zebrafish intestinal development and in tissue culture models of lumenogenesis. In conclusion, our data implicate the Rab11 effectors Fip5 and Fip1 in a trafficking pathway required for apical microvilli formation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping