研究激酶GCK-2及PKG-1對線蟲神經纖毛生成及鞭毛內運輸機制之影響調控

Cilia are specialized subcellular organelles which exist in various cell types in most eukaryotic organisms. Non-motile cilia, or primary cilia, are mainly responsible for sensory function and are recognized to have essential roles in physiology and development. Defects in ciliary proteins lead to severe diseases termed ciliopathies, such as polycystic kidney disease (PKD), the most common inherited kidney disease and one of the most life-threatening diseases in the world, or nephronophthisis (NPHP), the most common genetic cause of chronic kidney disease. The conserved bidirectional intraflagellar transport (IFT) is fundamentally involved in ciliogenesis and is coupled with multiple intracellular signaling pathways. Although significant advances have been made in understanding ciliogenesis and IFT in the past few years, details on how the process is regulated remains poorly understood. By genetic screening and chemotaxis assay, we have identified two kinases GCK-2 and PKG-1 which affect the chemo-sensibility of amphid neurons in C. elegans. In this study, we further characterize their regulation roles in ciliogenesis and IFT process by cilia length measurement and IFT motility analysis. Here, we observed that worms lacking GCK-2 tend to grow longer cilia. Later in the IFT analysis, the transport speeds of different IFT-components are affected in the absence of either GCK-2 or PKG-1. And the stable IFT machinery assembly may also be modulated by GCK-2 and PKG-1. In addition, we observed abnormal OSM-3 kinesin accumulation at the distal segment of cilia in pkg-1 mutant strains. Overall, here we reported that GCK-2 and PKG-1 may regulate ciliogenesis and IFT particle transport in different ways: GCK-2 controls cilia lengthening, while PKG-1 affects the association of OSM-3 kinesin to the retrograde IFT machinery.