Reduced expression of TAZ inhibits primary cilium formation in renal glomeruli

Abstract

Kidney cysts: Formation of signaling antennae The roles of two regulatory proteins in the kidneys have been further clarified and provide insights into cilia defects and cyst formation. Cilia are organelles that act as 'antennae' for cell signaling in many tissues. Recent studies have highlighted two proteins involved in kidney cilia formation, YAP and TAZ, but little is known about their roles. Jong Hoon Park and co-workers at Sookmyung Women's University in Seoul, South Korea, examined the role of TAZ in the regulation of kidney tubule cilia in mice. They explored the effects of silencing TAZ or YAP expression in different types of kidney tubule cells. TAZ deficiency but not YAP deficiency prevented correct cilia formation in the glomeruli, blood vessels that filter waste in the kidneys, and the resulting defects led to mild cyst generation. Renal primary cilia are antenna-like organelles that maintain cellular homeostasis via multiple receptors clustered along their membranes. Recent studies have revealed that YAP/TAZ, key paralogous effectors of the Hippo pathway, are involved in ciliogenesis; however, their independent roles need to be further investigated. Here, we analyzed the renal phenotypes of kidney-specific TAZ knockout mice and observed ciliary defects only in glomeruli where mild cysts were formed. This finding prompted us to verify the role of TAZ specifically in renal tubule ciliary regulation. Therefore, we investigated the effects of TAZ silencing and compared them to those of YAP knockdown using three different types of renal tubular cells. We found that the absence of TAZ prevented proper cilia formation in glomerular cells, whereas it had a negligible effect in collecting duct and proximal tubule cells. IFT and NPHP protein levels were altered because of TAZ deficiency, accompanied by ciliary defects in glomerular cells, and ciliary recovery was identified by regulating some NPHP proteins. Although our study focused on TAZ, ciliogenesis, and other ciliary genes, the results suggest the very distinct roles of YAP and TAZ in kidneys, specifically in terms of ciliary regulation.