Novel regulatory mechanism underlying biogenesis of the primary cilium, an antenna-like cellular organelle.
Primary cilia are cellular organelles projecting out from the cell surface and sensing diverse extracellular signals. Primary cilia are critical for embryonic development and adult tissue homeostasis. The present study identifies actin remodeling factors LIMK2 and TESK1 as dominant inhibitory regulators of the biogenesis of primary cilia. Transcriptional coactivator YAP appears to act downstream of LIMK2 and TESK1, suppressing the cilium assembly pathway.
Primary cilia exert a profound impact on cell signaling and cell cycle progression. Recently, actin cytoskeleton architecture has been recognized as a dominant regulatory input for primary cilium assembly, but the exact mechanism remain poorly understood. This study uncovers that actin cytoskeleton remodeling controls ciliogenesis by regulating the transcriptional coactivator YAP/TAZ, as well as ciliary vesicle trafficking. Cytoplasmic retention of YAP/TAZ correlates with active ciliogenesis, either in spatially confined cells or in cells treated with an actin filament destabilizer.
Moreover, knockdown of YAP/TAZ is sufficient to induce ciliogenesis, whereas YAP/TAZ hyperactivation suppresses serum starvation-mediated ciliogenesis.
This study also identifed actin remodeling factors LIMK2 and TESK1 as key upstream players in the ciliogenesis control network in which YAP/TAZ and directional vesicle trafficking are integral components. These results provide new insights for understanding the link between actin dynamics and ciliogenesis.
Jongshin Kim et al. Nature Communications 2015 6:6781
“Actin remodelling factors control ciliogenesis by regulating YAP/TAZ activity and vesicle trafficking”
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