Renal defects associated with improper polarization of the CRB and DLG polarity complexes in MALS-3 knockout mice
Autor: | Olsen, O, Funke, L, Long, JF, Fukata, M, Kazuta, T, Trinidad, JC, Moore, KA, Misawa, H, Welling, PA, Burlingame, AL, Zhang, M, Bredt, DS |
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Rok vydání: | 2007 |
Předmět: |
Kidney Disease
Knockout Organogenesis 1.1 Normal biological development and functioning Molecular Sequence Data Nerve Tissue Proteins Kidney Medical and Health Sciences Tight Junctions Mice Polycystic Kidney Disease parasitic diseases Genetics Animals Amino Acid Sequence Signal Transducing Adaptor Proteins Membrane Proteins Epithelial Cells Biological Sciences Protein Subunits Multiprotein Complexes Renal and Urogenital lipids (amino acids peptides and proteins) Cell Adhesion Molecules Sequence Alignment Developmental Biology |
Zdroj: | The Journal of cell biology, vol 179, iss 1 Olsen, O; Funke, L; Long, JF; Fukata, M; Kazuta, T; Trinidad, JC; et al.(2007). Renal defects associated with improper polarization of the CRB and DLG polarity complexes in MALS-3 knockout mice. Journal of Cell Biology, 179(1), 151-164. doi: 10.1083/jcb.200702054. UC San Francisco: Retrieved from: http://www.escholarship.org/uc/item/0p34w7qj |
Popis: | 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. © The Rockefeller University Press. |
Databáze: | OpenAIRE |
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