| Inactivation of Max Interacting Protein 1 Induces Renal Cilia Disassembly through Reduction in Levels of Intraflagellar Transport 20 in Polycystic Kidney. | |
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MedLine Citation:
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PMID: 23316056 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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)5. 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 (SEM) to elucidate the effect of Mxi1 on renal cilia phenotype and cilia disassembly was observed in Mxi1-deficient kidney. In addition, IFT genes were validated in vitro and in vivo using qPCR, 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. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2013-1-13 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Sookmyung Womens University, Korea, Republic of; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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