Mechanisms regulating cilia growth and cilia function in endothelial cells
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The primary cilium is an important sensory organelle present in most mammalian cells. Our current studies aim at examining intracellular molecules that regulate cilia length and/or cilia function in vitro and ex vivo. For the first time, we show that intracellular cAMP and cAMP-dependent protein kinase (PKA) regulate both cilia length and function in vascular endothelial cells. Although calcium-dependent protein kinase modulates cilia length, it does not play a significant role in cilia function. Cilia length regulation also involves mitogen-activated protein kinase (MAPK), protein phosphatase-1 (PP-1), and cofilin. Furthermore, cofilin regulates cilia length through actin rearrangement. Overall, our study suggests that the molecular interactions between cilia function and length can be independent of one another. Although PKA regulates both cilia length and function, changes in cilia length by MAPK, PP-1, or cofilin do not have a direct correlation to changes in cilia function. We propose that cilia length and function are regulated by distinct, yet complex intertwined signaling pathways.
KeywordsCalcium signaling Cardiovascular homeostasis Ciliopathy Fluid-shear stress Intraflagellar transport Mechanosensory cilium
The authors thank Dr. James Calvet for his scientific comments and Ms. Charisse Montgomery for her editorial review of the manuscript. S. Abdul-Majeed’s work partially fulfilled the requirements for a PhD degree in Medicinal and Biological Chemistry. This work was supported by the NIH grant DK080640 and the University of Toledo research programs.
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