PUBLICATION
Rab35 controls cilium length, function and membrane composition
- Authors
- Kuhns, S., Seixas, C., Pestana, S., Tavares, B., Nogueira, R., Jacinto, R., Ramalho, J.S., Simpson, J.C., Andersen, J.S., Echard, A., Lopes, S.S., Barral, D.C., Blacque, O.E.
- ID
- ZDB-PUB-190822-7
- Date
- 2019
- Source
- EMBO reports 20(10): e47625 (Journal)
- Registered Authors
- Lopes, Susana
- Keywords
- Arl13b, Rab35, Smoothened, cilia, left-right asymmetry
- MeSH Terms
-
- Animals
- Body Patterning
- Cell Line
- Cilia/metabolism*
- HEK293 Cells
- Humans
- Membranes/metabolism
- Mice
- Models, Biological
- NIH 3T3 Cells
- Nucleotides/metabolism
- Phosphatidylinositol 4,5-Diphosphate/metabolism*
- Protein Binding
- Protein Transport
- Telomerase/metabolism
- Zebrafish/metabolism*
- Zebrafish Proteins/metabolism*
- rab GTP-Binding Proteins/metabolism*
- PubMed
- 31432619 Full text @ EMBO Rep.
Citation
Kuhns, S., Seixas, C., Pestana, S., Tavares, B., Nogueira, R., Jacinto, R., Ramalho, J.S., Simpson, J.C., Andersen, J.S., Echard, A., Lopes, S.S., Barral, D.C., Blacque, O.E. (2019) Rab35 controls cilium length, function and membrane composition. EMBO reports. 20(10):e47625.
Abstract
Rab and Arl guanine nucleotide-binding (G) proteins regulate trafficking pathways essential for the formation, function and composition of primary cilia, which are sensory devices associated with Sonic hedgehog (Shh) signalling and ciliopathies. Here, using mammalian cells and zebrafish, we uncover ciliary functions for Rab35, a multitasking G protein with endocytic recycling, actin remodelling and cytokinesis roles. Rab35 loss via siRNAs, morpholinos or knockout reduces cilium length in mammalian cells and the zebrafish left-right organiser (Kupffer's vesicle) and causes motile cilia-associated left-right asymmetry defects. Consistent with these observations, GFP-Rab35 localises to cilia, as do GEF (DENND1B) and GAP (TBC1D10A) Rab35 regulators, which also regulate ciliary length and Rab35 ciliary localisation. Mammalian Rab35 also controls the ciliary membrane levels of Shh signalling regulators, promoting ciliary targeting of Smoothened, limiting ciliary accumulation of Arl13b and the inositol polyphosphate 5-phosphatase (INPP5E). Rab35 additionally regulates ciliary PI(4,5)P2 levels and interacts with Arl13b. Together, our findings demonstrate roles for Rab35 in regulating cilium length, function and membrane composition and implicate Rab35 in pathways controlling the ciliary levels of Shh signal regulators.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping