GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:20729296

From GONUTS
Jump to: navigation, search
Citation

Hurd, T, Zhou, W, Jenkins, P, Liu, CJ, Swaroop, A, Khanna, H, Martens, J, Hildebrandt, F and Margolis, B (2010) The retinitis pigmentosa protein RP2 interacts with polycystin 2 and regulates cilia-mediated vertebrate development. Hum. Mol. Genet. 19:4330-44

Abstract

Ciliopathies represent a growing group of human genetic diseases whose etiology lies in defects in ciliogenesis or ciliary function. Given the established entity of renal-retinal ciliopathies, we have been examining the role of cilia-localized proteins mutated in retinitis pigmentosa (RP) in regulating renal ciliogenesis or cilia-dependent signaling cascades. Specifically, this study examines the role of the RP2 gene product with an emphasis on renal and vertebrate development. We demonstrate that in renal epithelia, RP2 localizes to the primary cilium through dual acylation of the amino-terminus. We also show that RP2 forms a calcium-sensitive complex with the autosomal dominant polycystic kidney disease protein polycystin 2. Ablation of RP2 by shRNA promotes swelling of the cilia tip that may be a result of aberrant trafficking of polycystin 2 and other ciliary proteins. Morpholino-mediated repression of RP2 expression in zebrafish results in multiple developmental defects that have been previously associated with ciliary dysfunction, such as hydrocephalus, kidney cysts and situs inversus. Finally, we demonstrate that, in addition to our observed physical interaction between RP2 and polycystin 2, dual morpholino-mediated knockdown of polycystin 2 and RP2 results in enhanced situs inversus, indicating that these two genes also regulate a common developmental process. This work suggests that RP2 may be an important regulator of ciliary function through its association with polycystin 2 and provides evidence of a further link between retinal and renal cilia function.

Links

PubMed PMC2957320 Online version:10.1093/hmg/ddq355

Keywords

Acylation; Animals; Cilia/genetics; Cilia/metabolism; Cilia/physiology; Eye Proteins/metabolism; Gene Knockdown Techniques; Humans; Intracellular Signaling Peptides and Proteins/metabolism; Kidney/metabolism; Kidney/physiopathology; Kidney Diseases, Cystic/genetics; Kidney Diseases, Cystic/metabolism; Membrane Proteins/metabolism; Mutation; TRPP Cation Channels/metabolism; Vertebrates/genetics; Vertebrates/metabolism; Zebrafish/genetics; Zebrafish/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DANRE:XRP2

involved_in

GO:0048793: pronephros development

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-060630-4,ZFIN:ZDB-MRPHLNO-101122-2

P

Seeded From UniProt

complete

DANRE:XRP2

involved_in

GO:0048793: pronephros development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-101122-2

P

Seeded From UniProt

complete

DANRE:XRP2

involved_in

GO:0001947: heart looping

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-101122-2

P

Seeded From UniProt

complete

DANRE:PKD2

involved_in

GO:0048793: pronephros development

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-060630-4,ZFIN:ZDB-MRPHLNO-101122-2

P

Seeded From UniProt

complete

DANRE:Q6IVV8

involved_in

GO:0048793: pronephros development

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-060630-4
ZFIN:ZDB-MRPHLNO-101122-2

P

Seeded From UniProt

complete

DANRE:F1QC45

involved_in

GO:0048793: pronephros development

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-060630-4
ZFIN:ZDB-MRPHLNO-101122-2

P

Seeded From UniProt

complete

DANRE:F1QC45

involved_in

GO:0048793: pronephros development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-101122-2

P

Seeded From UniProt

complete

DANRE:F1QC45

involved_in

GO:0001947: heart looping

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-101122-2

P

Seeded From UniProt

complete

DANRE:Q2VF27

involved_in

GO:0048793: pronephros development

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-060630-4
ZFIN:ZDB-MRPHLNO-101122-2

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.