Document Detail

Inactivation of max-interacting protein 1 induces renal cilia disassembly through reduction in levels of intraflagellar transport 20 in polycystic kidney.
MedLine Citation:
PMID:  23316056     Owner:  NLM     Status:  MEDLINE    
Cilia in ciliated cells consist of protruding structures that sense mechanical and chemical signals from the extracellular environment. Cilia are assembled with variety molecules via a process known as intraflagellar transport (IFT). What controls the length of cilia in ciliated cells is critical to understand ciliary disease such as autosomal dominant polycystic kidney disease, which involves abnormally short cilia. But this control mechanism is not well understood. Previously, multiple tubular cysts have been observed in the kidneys of max-interacting protein 1 (Mxi1)-deficient mice aged 6 months or more. Here, we clarified the relationship between Mxi1 inactivation and cilia disassembly. Cilia phenotypes were observed in kidneys of Mxi1-deficient mice using scanning electron microscopy to elucidate the effect of Mxi1 on renal cilia phenotype, and cilia disassembly was observed in Mxi1-deficient kidney. In addition, genes related to cilia were validated in vitro and in vivo using quantitative PCR, and Ift20 was selected as a candidate gene in this study. The length of cilium decreased, and p-ERK level induced by a cilia defect increased in kidneys of Mxi1-deficient mice. Ciliogenesis of Mxi1-deficient mouse embryonic fibroblasts (MEFs) decreased, and this abnormality was restored by Mxi1 transfection in Mxi1-deficient MEFs. We confirmed that ciliogenesis and Ift20 expression were regulated by Mxi1 in vitro. We also determined that Mxi1 regulates Ift20 promoter activity via Ets-1 binding to the Ift20 promoter. These results indicate that inactivating Mxi1 induces ciliary defects in polycystic kidney.
Je Yeong Ko; Kyung Hyun Yoo; Seon Ah Song; Do Yeon Kim; Hyun Kyung Kong; Curie Ahn; Han Woong Lee; Duk-Hee Kang; Goo Taeg Oh; Jong Hoon Park
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-13
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  288     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-04     Completed Date:  2013-05-09     Revised Date:  2014-03-06    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6488-97     Citation Subset:  IM    
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MeSH Terms
Basic Helix-Loop-Helix Transcription Factors / genetics,  metabolism*
Carrier Proteins / biosynthesis*,  genetics
Cells, Cultured
Cilia / metabolism,  ultrastructure
Embryo, Mammalian / metabolism,  ultrastructure
Fibroblasts / metabolism,  ultrastructure
Gene Expression Regulation / genetics
Kidney / metabolism*,  ultrastructure
Mice, Mutant Strains
Microscopy, Electron, Scanning
Polycystic Kidney, Autosomal Dominant / genetics,  metabolism*,  pathology
Polymerase Chain Reaction
Proto-Oncogene Protein c-ets-1 / genetics,  metabolism
Response Elements / genetics
Tumor Suppressor Proteins / genetics,  metabolism*
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/Carrier Proteins; 0/Ets1 protein, mouse; 0/Ift20 protein, mouse; 0/Mxi1 protein, mouse; 0/Proto-Oncogene Protein c-ets-1; 0/Tumor Suppressor Proteins

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