Combined deletion of Vhl, Trp53 and Kif3a
causes cystic and neoplastic renal lesions.
The transport of ciliary proteins from the cytoplasm to the ciliary tip, known as anterograde transport, depends on the heterotrimeric kinesin-2 protein, which consists of two motor subunits, KIF3A and KIF3B, and an accessory subunit, the kinesin-associated protein (KAP) .
The same results were also obtained in KECs following the knockdown of KIF3A when exposed to increased fluid flow, suggesting that the PC is required for fluid flow-induced autophagy .
KIF3A-deficient mice, where KIF3A is selectively depleted in tubular cells, exhibited impaired ciliogenesis, reduced autophagy, and larger tubular epithelial cells than control mice.
First, the authors demonstrated that the inducible systemic deletion of KIF3A and Tg737 (mouse homologue of iFt88) produces PC loss in adult mice.
Tissue sections from the corresponding FFPE tissue blocks were placed on slides, underwent high pH antigen retrieval, and were subsequently incubated with one of the following primary antibodies: mouse monoclonal anti-human keratin 20 (prediluted, Dako IS777), mouse monoclonal anti-human mucin 1 (1 : 100, Leica, NCL-HGM-45mL), and rabbit polyclonal anti-human KIT (1 : 250, Dako A4502), rabbit polyclonal anti-human KIF3A (1 : 1200, Sigma K3513).
Immunohistochemistry was utilized to examine the protein products of MUC1, KIT, KIF3A, and KRT20 (Table 3).
In addition to these genes, there were other genes that were of interest and associated with cancer development or progression including dimethylarginine dimethylaminohydrolase 1 (DDAH1), kinesin family member 3A (KIF3A), and MUC1 which are all upregulated in the poor prognosis samples.
Unlike the positive results with KRT20, protein levels of KIF3A and MUC1 did not display a positive association with gene expression results.
In Kif3a knock-out mice precystic tubules appeared to have irregular planar cell polarity, indicating that primary cilia are required for its maintenance.
Kidney-specific inactivation of the KIF3A subunit of kinesin-II inhibits renal ciliogenesis and produces polycystic kidney disease.