| Normal ciliogenesis requires synergy between the cystic kidney disease genes MKS-3 and NPHP-4. | |
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MedLine Citation:
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PMID: 20150540 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cilia dysfunction contributes to renal cyst formation in multiple human syndromes including nephronophthisis (NPHP), Meckel-Gruber syndrome (MKS), Joubert syndrome (JBTS), and Bardet-Beidl syndrome (BBS). Although genetically heterogeneous, these diseases share several loci that affect cilia and/or basal body proteins, but the functions and interactions of these gene products are incompletely understood. Here, we report that the ciliated sensory neurons (CSNs) of C. elegans express the putative transmembrane protein MKS-3, which localized to the distal end of their dendrites and to the cilium base but not to the cilium itself. Localization of MKS-3 and other known MKS and NPHP proteins partially overlapped. By analyzing mks-3 mutants, we found that ciliogenesis did not require MKS-3; instead, cilia elongated and cilia-mediated chemoreception was abnormal. Genetic analysis indicated that mks-3 functions in a pathway with other mks genes. Furthermore, mks-1 and mks-3 genetically interacted with a separate pathway (involving nphp-1 and nphp-4) to influence proper positioning, orientation, and formation of cilia. Combined disruption of nphp and mks pathways had cell nonautonomous effects on C. elegans sensilla. Taken together, these data demonstrate the importance of mutational load on the presentation and severity of ciliopathies and expand the understanding of the interactions between ciliopathy genes. |
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Authors:
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Corey L Williams; Svetlana V Masyukova; Bradley K Yoder |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-02-11 |
Journal Detail:
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Title: Journal of the American Society of Nephrology : JASN Volume: 21 ISSN: 1533-3450 ISO Abbreviation: J. Am. Soc. Nephrol. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-03 Completed Date: 2010-06-21 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 9013836 Medline TA: J Am Soc Nephrol Country: United States |
Other Details:
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Languages: eng Pagination: 782-93 Citation Subset: IM |
Affiliation:
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Department of Cell Biology, University of Alabama at Birmingham Medical Center, Birmingham, Alabama, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alleles Animals Caenorhabditis elegans Caenorhabditis elegans Proteins / chemistry, genetics, metabolism* Chemotaxis Cilia / metabolism Gene Expression Regulation Kidney Diseases, Cystic / genetics, metabolism Membrane Proteins / chemistry, genetics, metabolism* Sensory Receptor Cells / metabolism Transcription Factors / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 DK065655/DK/NIDDK NIH HHS; R01 DK62758/DK/NIDDK NIH HHS; T32 DK007545-22/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Caenorhabditis elegans Proteins; 0/DAF-19 protein, C elegans; 0/MKS-3 protein, C elegans; 0/Membrane Proteins; 0/Transcription Factors; 0/nephrocystin 4, C elegans |
| Comments/Corrections | |
Comment In:
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J Am Soc Nephrol. 2010 May;21(5):724-6
[PMID:
20395369
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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