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Podocyte biology

A new regulator of podocytes

Nature Reviews Nephrology volume 8, page 683 (2012)Cite this article

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Two main cognate receptor tyrosine kinases for VEGF exist—FLK1/KDR and FLT1. FLK1/KDR mediates most of the angiogenic functions of VEGF, but the functions of FLT1 are poorly understood. FLT1 exists as both a soluble, truncated form (sFLT1) and as a full-length isoform. “We had previously shown that VEGF production by podocytes is crucial for the maintenance of the glomerular endothelium but were keen to know if there were any additional roles for the VEGF receptors or involvement of autocrine signalling”, says Quaggin. “We therefore sequentially deleted all of the VEGF receptors from podocytes and discovered a profound phenotype when we knocked out Flt1.”

Quaggin and colleagues found that podocyte-specific deletion of Flt1 in mice resulted in marked reorganization of podocyte architecture and proteinuria. This effect was independent of Flt1 kinase function as the presence of a kinase-deficient Flt1 allele rescued the phenotype. To determine whether the podocyte changes resulted from altered sFlt1 expression, the researchers performed culture studies to examine the effects of sFLT1 on human podocytes. sFLT1 promoted podocyte attachment and rapid cytoskeletal reorganization. As Quaggin explains, “at this point, we proposed a new model—that sFLT1 might function as a 'ligand' to effect podocyte function—and set out to find the 'receptor'.”

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ORIGINAL RESEARCH PAPER

  1. Jin, J. et al. Soluble FLT1 binds lipid microdomains in podocytes to control cell morphology and glomerular barrier function. Cell 151, 384–399 (2012)

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Authors
  1. Susan J. Allison
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Allison, S. A new regulator of podocytes. Nat Rev Nephrol 8, 683 (2012). https://doi.org/10.1038/nrneph.2012.231

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  • DOI: https://doi.org/10.1038/nrneph.2012.231

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