Inactivation of max-interacting protein 1 induces renal cilia disassembly through reduction in levels of intraflagellar transport 20 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

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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. Wealso 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.

Original languageEnglish
Pages (from-to)6488-6497
Number of pages10
JournalJournal of Biological Chemistry
Volume288
Issue number9
DOIs
Publication statusPublished - 2013 Mar 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Inactivation of max-interacting protein 1 induces renal cilia disassembly through reduction in levels of intraflagellar transport 20 in polycystic kidney'. Together they form a unique fingerprint.

  • Cite this