ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3

被引：164

作者：

Hoff, Sylvia ^{[1
,2
,3
]}

Halbritter, Jan ^{[4
]}

Epting, Daniel ^{[1
]}

Frank, Valeska ^{[5
]}

Nguyen, Thanh-Minh T. ^{[6
,7
]}

van Reeuwijk, Jeroen ^{[6
,7
]}

Boehlke, Christopher ^{[1
]}

Schell, Christoph ^{[1
,2
,3
]}

Yasunaga, Takayuki ^{[1
]}

Helmstaedter, Martin ^{[1
,3
]}

Mergen, Miriam ^{[1
]}

Filhol, Emilie ^{[8
,9
]}

Boldt, Karsten ^{[10
,11
]}

Horn, Nicola ^{[10
,11
]}

Ueffing, Marius ^{[10
,11
,12
,13
]}

Otto, Edgar A. ^{[14
]}

Eisenberger, Tobias ^{[5
]}

Elting, Mariet W. ^{[15
]}

van Wijk, Joanna A. E. ^{[16
]}

Bockenhauer, Detlef ^{[17
]}

Sebire, Neil J. ^{[18
]}

Rittig, Soren ^{[19
]}

Vyberg, Mogens ^{[20
]}

Ring, Troels ^{[21
]}

Pohl, Martin ^{[22
]}

Pape, Lars ^{[23
]}

Neuhaus, Thomas J. ^{[24
]}

Elshakhs, Neveen A. Soliman ^{[25
,26
]}

Koon, Sarah J. ^{[27
]}

Harris, Peter C. ^{[27
]}

Grahammer, Florian ^{[1
]}

Huber, Tobias B. ^{[1
,28
]}

Kuehn, E. Wolfgang ^{[1
,28
]}

Kramer-Zucker, Albrecht ^{[1
]}

Bolz, Hanno J. ^{[5
,29
]}

Roepman, Ronald ^{[6
,7
]}

Saunier, Sophie ^{[8
,9
]}

Walz, Gerd ^{[1
,28
]}

Hildebrandt, Friedhelm ^{[4
,30
]}

Bergmann, Carsten ^{[1
,5
,31
]}

Lienkamp, Soeren S. ^{[1
]}

机构：

[1] Univ Freiburg, Dept Med, Div Renal, Med Ctr, Freiburg, Germany

[2] Univ Freiburg, Spemann Grad Sch Biol & Med SGBM, D-79106 Freiburg, Germany

[3] Univ Freiburg, Fac Biol, D-79106 Freiburg, Germany

[4] Harvard Univ, Sch Med, Dept Med, Boston Childrens Hosp, Boston, MA 02114 USA

[5] Bioscientia, Ctr Human Genet, Ingelheim, Germany

[6] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mol Life Sci, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands

[7] Radboud Univ Nijmegen, Med Ctr, Inst Genet & Metab Dis, NL-6525 ED Nijmegen, Netherlands

[8] Hop Necker Enfants Malad, INSERM, U983, Paris, France

[9] Paris Descartes Sorbonne Paris Cite Univ, Imagine Inst, Paris, France

[10] Univ Tubingen, Inst Ophthalm Res, Div Expt Ophthalmol, Tubingen, Germany

[11] Univ Tubingen, Med Proteome Ctr, Tubingen, Germany

[12] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Prot Sci, Munich, Germany

[13] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Prot Sci, Neuherberg, Germany

[14] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA

[15] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Amsterdam, Netherlands

[16] Vrije Univ Amsterdam Med Ctr, Dept Pediat Nephrol, Amsterdam, Netherlands

[17] UCL, Inst Child Hlth & Pediat Nephrol, Great Ormond St Hosp, London, England

[18] Great Ormond St Hosp Sick Children, Dept Histopathol, London WC1N 3JH, England

[19] Aarhus Univ Hosp, Dept Pediat, DK-8000 Aarhus, Denmark

[20] Aalborg Univ Hosp, Inst Pathol, Aalborg, Denmark

[21] Aalborg Univ Hosp, Dept Nephrol, Aalborg, Denmark

[22] Univ Freiburg, Med Ctr, Dept Pediat & Adolescent Med, Freiburg, Germany

[23] Hannover Med Sch, Dept Pediat Nephrol, Hannover, Germany

[24] Childrens Hosp Lucerne, Dept Pediat, Luzern, Switzerland

[25] Cairo Univ, Ctr Pediat Nephrol & Transplantat, Cairo, Egypt

[26] EGORD, Cairo, Egypt

[27] Mayo Clin, Div Nephrol & Hypertens, Rochester, MN USA

[28] Ctr Biol Signaling Studies BIOSS, Freiburg, Germany

[29] Univ Hosp Cologne, Inst Human Genet, Cologne, Germany

[30] Howard Hughes Med Inst, Chevy Chase, MD USA

[31] Univ Freiburg, Clin Res Ctr, D-79106 Freiburg, Germany

来源：

NATURE GENETICS | 2013年 / 45卷 / 08期

基金：

美国国家卫生研究院;

关键词：

POLYCYSTIC KIDNEY-DISEASE; TANDEM AFFINITY PURIFICATION; PROTEIN COMPLEXES; ZEBRAFISH; CILIARY; PRONEPHROS; CILIOPATHIES; MUTATIONS; GENES; NEPHROCYSTIN-3;

D O I：

10.1038/ng.2681

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Nephronophthisis is an autosomal recessive cystic kidney disease that leads to renal failure in childhood or adolescence. Most NPHP gene products form molecular networks. Here we identify ANKS6 as a new NPHP family member that connects NEK8 (NPHP9) to INVS (NPHP2) and NPHP3. We show that ANKS6 localizes to the proximal cilium and confirm its role in renal development through knockdown experiments in zebrafish and Xenopus laevis. We also identify six families with ANKS6 mutations affected by nephronophthisis, including severe cardiovascular abnormalities, liver fibrosis and situs inversus. The oxygen sensor HIF1AN hydroxylates ANKS6 and INVS and alters the composition of the ANKS6-INVS-NPHP3 module. Knockdown of Hif1an in Xenopus results in a phenotype that resembles loss of other NPHP proteins. Network analyses uncovered additional putative NPHP proteins and placed ANKS6 at the center of this NPHP module, explaining the overlapping disease manifestation caused by mutation in ANKS6, NEK8, INVS or NPHP3.

引用

页码：951 / U160

页数：8

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