Glomerular mesangial cell recruitment and function require the co-receptor neuropilin-1

Christina S. Bartlett, Rizaldy P. Scott, Isabel Anna Carota, Monika L. Wnuk, Yashpal S. Kanwar, Jeffrey H. Miner, Susan E. Quaggin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Proteinuria has been reported in cancer patients receiving agents that target the transmembrane receptor neuropilin-1 (Nrp1) suggesting potential adverse effects on glomerular function. Here we show that Nrp1 is highly expressed by mesangial cells and that genetic deletion of the Nrp1 gene from PDGF receptor-β+ mesangial cells results in proteinuric disease and glomerulosclerosis, leading to renal failure and death within 6 wk of age in mice. The major defect is a failure of mesangial cell migration that is required to establish the mature glomerular tuft. In vitro data show that the potent chemotactic effect of PDGFB is lost in Nrp1-deficient mesangial cells. Biochemical analyses reveal that Nrp1 is required for PDGFB-dependent phosphorylation of p130 Crk-associated substrate (p130Cas), a large-scaffold molecule that is involved in motility of other cell types. In stark contrast, matrix adhesion and activation of ERK and Akt, which mediate proliferation of mesangial cells in response to PDGFB, are unaffected by the absence of Nrp1. Taken together, these results identify a critical cell-autonomous role for Nrp1 in the migratory behavior of mesangial cells and may help explain the renal effects that occur in patients receiving Nrp1-inhibitory drugs.

Original languageEnglish (US)
Pages (from-to)F1232-F1242
JournalAmerican Journal of Physiology - Renal Physiology
Issue number6
StatePublished - Dec 2017


  • Cell migration
  • Glomerulosclerosis
  • Mesangial cells
  • Neuropilin
  • Proteinuria

ASJC Scopus subject areas

  • Urology
  • Physiology


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