Renal defects associated with improper polarization of the CRB and DLG polarity complexes in MALS-3 knockout mice

Olav Olsen, Lars Funke, Jia Fu Long, Masaki Fukata, Toshinari Kazuta, Jonathan C. Trinidad, Kimberly A. Moore, Hidemi Misawa, Paul A. Welling, Alma L. Burlingame, Mingjie Zhang, David S. Bredt

研究成果: Article査読

36 被引用数 (Scopus)

抄録

Kidney development and physiology require polarization of epithelia that line renal tubules. Genetic studies show that polarization of invertebrate epithelia requires the crumbs, partition-defective-3, and discs large complexes. These evolutionarily conserved protein complexes occur in mammalian kidney; however, their role in renal development remains poorly defined. Here, we find that mice lacking the small PDZ protein mammalian LIN-7c (MALS-3) have hypomorphic, cystic, and fibrotic kidneys. Proteomic analysis defines MALS-3 as the only known core component of both the crumbs and discs large cell polarity complexes. MALS-3 mediates stable assembly of the crumbs tight junction complex and the discs large basolateral complex, and these complexes are disrupted in renal epithelia from MALS-3 knockout mice. Interestingly, MALS-3 controls apico-basal polarity preferentially in epithelia derived from metanephric mesenchyme, and defects in kidney architecture owe solely to MALS expression in these epithelia. These studies demonstrate that defects in epithelial cell polarization can cause cystic and fibrotic renal disease.

本文言語English
ページ(範囲)151-164
ページ数14
ジャーナルJournal of Cell Biology
179
1
DOI
出版ステータスPublished - 2007 10月 8
外部発表はい

ASJC Scopus subject areas

  • 細胞生物学

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