title: Inactivation of max-interacting protein 1 induces renal cilia disassembly through reduction in levels of intraflagellar transport 20 in polycystic kidney.
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. 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.
authors: From the Department of Biological Science, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors: Je Yeong
authors: JY
authors: Ko
authors: Kyung Hyun
authors: KH
authors: Yoo
authors: Seon Ah
authors: SA
authors: Song
authors: Do Yeon
authors: DY
authors: Kim
authors: Hyun Kyung
authors: HK
authors: Kong
authors: Curie
authors: C
authors: Ahn
authors: Han Woong
authors: HW
authors: Lee
authors: Duk-Hee
authors: DH
authors: Kang
authors: Goo Taeg
authors: GT
authors: Oh
authors: Jong Hoon
authors: JH
authors: Park
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D002923:Cilia / Q000378:metabolism / Q000648:ultrastructure; D004622:Embryo, Mammalian / Q000378:metabolism / Q000648:ultrastructure; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000235:genetics; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008817:Mice, Mutant Strains; D008855:Microscopy, Electron, Scanning; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002352:Carrier Proteins; D050784:Proto-Oncogene Protein c-ets-1; D025521:Tumor Suppressor Proteins; C494042:Ets1 protein, mouse; C514104:Ift20 protein, mouse; C512788:Mxi1 protein, mouse