PUBLICATION
Prominins control ciliary length throughout the animal kingdom: New lessons from human prominin-1 and zebrafish prominin-3
- Authors
- Jászai, J., Thamm, K., Karbanová, J., Janich, P., Fargeas, C.A., Huttner, W.B., Corbeil, D.
- ID
- ZDB-PUB-200403-154
- Date
- 2020
- Source
- The Journal of biological chemistry 295(18): 6007-6022 (Journal)
- Registered Authors
- Keywords
- ADP ribosylation factor (ARF), Arl13b, CD133, MDCK, cilia, development, left-right asymmetry, membrane polarity, membrane protein, prominin-1, zebrafish
- MeSH Terms
-
- AC133 Antigen/chemistry
- AC133 Antigen/genetics
- AC133 Antigen/metabolism*
- Animals
- Cilia/metabolism*
- Dogs
- Down-Regulation
- Gene Expression Regulation, Developmental
- Intracellular Space/metabolism
- Kupffer Cells/cytology
- Madin Darby Canine Kidney Cells
- Mutation
- Protein Transport
- Tyrosine
- Zebrafish*
- PubMed
- 32201384 Full text @ J. Biol. Chem.
Citation
Jászai, J., Thamm, K., Karbanová, J., Janich, P., Fargeas, C.A., Huttner, W.B., Corbeil, D. (2020) Prominins control ciliary length throughout the animal kingdom: New lessons from human prominin-1 and zebrafish prominin-3. The Journal of biological chemistry. 295(18):6007-6022.
Abstract
Prominins (proms) are transmembrane glycoproteins conserved throughout the animal kingdom. They are associated with plasma membrane protrusions, such as primary cilia, as well as extracellular vesicles derived thereof. Primary cilia host numerous signaling pathways affected in diseases known as ciliopathies. Human PROM1 (CD133) is detected in both somatic and cancer stem cells and is also expressed in terminally differentiated epithelial and photoreceptor cells. Genetic mutations in the PROM1 gene result in retinal degeneration by impairing the proper formation of the outer segment of photoreceptors, a modified cilium. Here, we investigated the impact of proms on two distinct examples of ciliogenesis. First, we demonstrate that the overexpression of a dominant-negative mutant variant of human PROM1 (i.e. mutation Y819F/Y828F) significantly decreases ciliary length in Madin-Darby canine kidney cells. These results contrast strongly to the previously observed enhancing effect of wild-type PROM1 on ciliary length. Mechanistically, the mutation impeded the interaction of PROM1 with ADP-ribosylation factor-like protein 13B, a key regulator of ciliary length. Second, we observed that in vivo knockdown of prom3 in zebrafish alters the number and length of monocilia in the Kupffer's vesicle, resulting in molecular and anatomical defects in the left-right asymmetry. These distinct loss-of-function approaches in two biological systems reveal that prom proteins are critical for the integrity and function of cilia. Our data provide new insights in ciliogenesis and might be of particular interest for investigations of the etiologies of ciliopathies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping