Scribble participates in Hippo signaling and is required for normal zebrafish pronephros development

被引：126

作者：

Skouloudaki, Kassiani ^{[1
]}

Puetz, Michael ^{[1
]}

Simons, Matias ^{[2
]}

Courbard, Jean-Remy ^{[2
]}

Boehlke, Christopher ^{[1
]}

Hartleben, Bjoern ^{[1
]}

Engel, Christina ^{[1
]}

Moeller, Marcus J. ^{[3
]}

Englert, Christoph ^{[4
]}

Bollig, Frank ^{[4
]}

Schaefer, Tobias ^{[1
]}

Ramachandran, Haribaskar ^{[1
]}

Mlodzik, Marek ^{[2
]}

Huber, Tobias B. ^{[1
]}

Kuehn, E. Wolfgang ^{[1
]}

Kim, Emily ^{[1
]}

Kramer-Zucker, Albrecht ^{[1
]}

Walz, Gerd ^{[1
,5
]}

机构：

[1] Univ Hosp Freiburg, Div Renal, D-79106 Freiburg, Germany

[2] Mt Sinai Sch Med, Dept Dev & Regenerat Biol, New York, NY 10029 USA

[3] Rhein Westfal TH Aachen, Div Nephrol, D-52074 Aachen, Germany

[4] Age Res Fritz Lipmann Inst, Leibniz Inst, D-07745 Jena, Germany

[5] Ctr Biol Signaling Studies Bioss, D-79104 Freiburg, Germany

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 21期

基金：

美国国家卫生研究院;

关键词：

Fat; planar cell polarity; polycystic kidney disease; POLYCYSTIC KIDNEY-DISEASE; TUMOR-SUPPRESSOR PATHWAY; CELL POLARIZATION; MIGRATION; FAT; POLARITY; GROWTH; DEFECTS; TAZ; DROSOPHILA;

D O I：

10.1073/pnas.0811691106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Spatial organization of cells and their appendages is controlled by the planar cell polarity pathway, a signaling cascade initiated by the protocadherin Fat in Drosophila. Vertebrates express 4 Fat molecules, Fat1-4. We found that depletion of Fat1 caused cyst formation in the zebrafish pronephros. Knockdown of the PDZ domain containing the adaptor protein Scribble intensified the cyst-promoting phenotype of Fat1 depletion, suggesting that Fat1 and Scribble act in overlapping signaling cascades during zebrafish pronephros development. Supporting the genetic interaction with Fat1, Scribble recognized the PDZ-binding site of Fat1. Depletion of Yes-associated protein 1 (YAP1), a transcriptional co-activator inhibited by Hippo signaling, ameliorated the cyst formation in Fat1-deficient zebrafish, whereas Scribble inhibited the YAP1-induced cyst formation. Thus, reduced Hippo signaling and subsequent YAP1 disinhibition seem to play a role in the development of pronephric cysts after depletion of Fat1 or Scribble. We hypothesize that Hippo signaling is required for normal pronephros development in zebrafish and that Scribble is a candidate link between Fat and the Hippo signaling cascade in vertebrates.

引用

页码：8579 / 8584

页数：6

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