Abstract
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.
Highlights
Primary cilia are sensory organelles that act as antennae to transmit signals within and outside the cell
In podocytes labeled with recovered at 24 h, when cilia were fully assembled, but its expression trend was the opposite in TKPTS cells. These results suggest that transcriptional coactivator with PDZ-binding motif (TAZ) localized near primary cilia participates in cilia formation and that this process is dependent on the type of renal tubule cell
Renal primary ciliary defects are caused by genetic mutations and are associated with renal tubular cyst formation
Summary
Primary cilia are sensory organelles that act as antennae to transmit signals within and outside the cell. There are two major types of cilia, namely, motile and nonmotile cilia, both of which are alpha- and beta-tubulin microtubule-based organelles and are composed of an axoneme of 9 doublet microtubules[1]. To better understand the structure of primary cilia, we focused on the axoneme, transition zones, and basal body. After a distal appendage of the basal body is anchored to the membrane, a ciliary pocket is formed to assemble the axoneme, which is used in transport of the intraflagellar complex. Kinesin-2 transports cargo proteins such as intraflagellar transport (IFT) complex B to the ciliary tip and, upon cell cycle reentry, the dynein-2 retrograde IFT complex A is transported from the ciliary tip to the base of the cilium, causing the primary cilium structure to disassemble. IFT proteins regulate ciliary assembly and transport proteins to maintain homeostasis[2]
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