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

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)151-164
Number of pages14
JournalJournal of Cell Biology
Volume179
Issue number1
DOIs
Publication statusPublished - 2007 Oct 8

ASJC Scopus subject areas

  • Cell Biology

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