PUBLICATION
Anks3 interacts with nephronophthisis proteins and is required for normal renal development
- Authors
- Yakulov, T.A., Yasunaga, T., Ramachandran, H., Engel, C., Müller, B., Hoff, S., Dengjel, J., Lienkamp, S.S., Walz, G.
- ID
- ZDB-PUB-150212-1
- Date
- 2015
- Source
- Kidney International 87(6): 1191-200 (Journal)
- Registered Authors
- Ramachandran, Hari
- Keywords
- ankyrin-repeat proteins, ciliopathies, nephronophthisis, renal development
- MeSH Terms
-
- Humans
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- Adaptor Proteins, Signal Transducing/metabolism
- Gene Knockdown Techniques
- Polymerization
- Xenopus Proteins/genetics
- Xenopus Proteins/metabolism*
- Nuclear Proteins/metabolism
- Repressor Proteins/metabolism
- Animals
- Proteins/metabolism
- Carrier Proteins/genetics*
- Carrier Proteins/metabolism*
- Membrane Proteins/metabolism
- NIMA-Related Kinases
- Situs Inversus/genetics
- RNA-Binding Proteins/metabolism
- HEK293 Cells
- Zebrafish
- Kidney Diseases, Cystic/metabolism
- Mixed Function Oxygenases/metabolism
- Kidney/abnormalities
- Kidney/embryology*
- Xenopus
- Cilia/metabolism
- Protein Kinases/metabolism
- PubMed
- 25671767 Full text @ Kidney Int.
Citation
Yakulov, T.A., Yasunaga, T., Ramachandran, H., Engel, C., Müller, B., Hoff, S., Dengjel, J., Lienkamp, S.S., Walz, G. (2015) Anks3 interacts with nephronophthisis proteins and is required for normal renal development. Kidney International. 87(6):1191-200.
Abstract
Nephronophthisis (NPH) is a heterogenetic autosomal recessive disorder associated with kidney cysts and multiple extrarenal manifestations. The disease-associated gene products (NPHPs) typically contain domains involved in protein-protein interactions, and appear to exert their tissue-specific functions in large protein complexes. Most NPHPs localize to the cilium and/or basal body; however, their precise molecular functions remain largely unknown. We have recently identified the SAM-domain containing protein Anks3 as a potential ANKS6/NPHP16-interacting protein, and report now that Anks3 interacts with several NPHPs as well as with Bicc1 and the oxygen-sensitive asparaginyl hydroxylase HIF1AN. Knockdown of anks3 in zebrafish embryos was associated with NPH-typical manifestations, including ciliary abnormalities, cyst formation, and laterality defects. In multi-ciliated epidermal cells, GFP-tagged Anks3 localizes to the cilium, but forms large aggregates in the absence of NPHP1, indicating that the negatively charged NPHP1 curtails the polymerization of Anks3. Collectively, these findings suggest that Anks3 is a cilia-associated molecule that partners with the ANKS6- and via NPHP1 to the NPHP1-4-8 module. Thus, developmental defects associated with Anks3 depletion in zebrafish suggest that ANKS3 mutations may cause NPH or NPH-like disease in humans.Kidney International advance online publication, 11 February 2015; doi:10.1038/ki.2015.17.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping