Abstract: SA-PO202

Loss of Function of Rhpn1 Leads to Proteinuria through Downregulation of Wt1 via Wtip

Session Information

  • Glomerular: Cell Biology
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Glomerular

  • 1003 Glomerular: Cell Biology

Author

  • Katayama, Kan, Mie university graduate school of medicine, Tsu, Japan
Background

Rhophilin-1, Rhpn1 was identified as one of podocyte-enriched proteins and Rhpn1 inactivation in mice showed proteinuria at an early stage. Although the onset of proteinuria was suggested by a mechanism due to the altered actin cytoskeleton structure, the underlying pathogenesis is not fully clarified. Moreover, there is no report in human so far.

Methods

Therefore, we investigated the function of rhpn1 in zebrafish to evaluate whether the phenotypic change was conserved in zebrafish.

Results

Knockdown of rhpn1 in zebrafish caused proteinuria, which was confirmed by the uptake of 500 kDa Fluorescein isothiocyanate-conjugated dextran in proximal tubules. To further analyze the function of Rhpn1, yeast two hybrid screening was performed and Wilms tumor protein 1-interacting protein, Wtip, was identified as an interaction partner of Rhpn1. rhpn1 knockdown in zebrafish or Rhpn1 knockout in mouse resulted in downregulation of mRNA of Wilms tumor protein 1, WT1. In kidneys from Rhpn1 knockout mouse, nuclear translocation of Wtip protein was observed more commonly compared to wild-type mouse kidneys.

Conclusion

Taken together, loss of interaction between Rhpn1 and Wtip might be involved in the development of proteinuria through downregulation of Wt1.