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

By H. Kim, Yong Sun Lee, U. Sivaprasad, Ankit Malhotra, Anindya Dutta. Journal of Cell Biology, 2007

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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.

Subfields: Genetics, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/970d3512d82694e5273842899afe15d9c498411a

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Making muscle: skeletal myogenesis in vivo and in vitro (2017, background): “Additionally, a number of microRNAs (miRNAs) are highly expressed, often specifically, in muscle cells (Chen et al., 2006; Kim et al., 2006; Sweetman et al., 2008).”
microRNA-1 and microRNA-206 regulate skeletal muscle satellite cell proliferation and differentiation by repressing Pax7 (2010, background): “We and others previously demonstrated that miR-1 and miR-206 promote skeletal muscle terminal differentiation (Chen et al., 2006; Kim et al., 2006; Rosenberg et al., 2006; Williams et al., 2009).”
MicroRNAs in development and disease. (2011, background): “Additional direct targets that were validated for miR206 include the p180 subunit of the DNA polymerase -subunit (299), whose downregulation coincides with cell cycle exit and differentiation of various tissues (252).”
A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). (2009, background): “Source of tissue RNAs is described in Kim et al. (2006). tRF-1001 (19-mer) is indicated by an arrowhead on the left.”
MEF2: a central regulator of diverse developmental programs (2007, background): “Recently, several microRNAs were identified that affect skeletal muscle differentiation and proliferation (Boutz et al., 2007; Chen et al., 2006; Kim et al., 2006; Rao et al., 2006).”
The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. (2007, result): “The distributed pattern of the 5 ends of degradation products is similar to our previous results with another miRNA, miR-206 (Kim et al. 2006), and is consistent with the notion that the mRNA is degraded by exonucleases (with pause sites) instead of by a miRNA directed site-specific…”
Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. (2007, background): “Consistent with our findings, overexpression of miR-1 and the related miR-206 in skeletal myoblasts results in inhibition of DNA synthesis and withdrawal from the cell cycle (Kim et al., 2006).”