Adenylyl Cyclase 6 Mediates Primary Cilia-Dependent Changes in Cyclic Adenosine Monophosphate in Response to Dynamic Fluid Flow

It is well accepted that fluid flow is an important mechanical signal in regulating bone structure and function. Primary cilia, which are solitary, microtubule-based organelles that extend from the centrosome into extracellular space in many cell types, have been shown to mediate fluid flow-induced osteogenic responses in MLO-Y4 osteocyte-like cells [1], however, primary cilia did not mediate increases in intracellular Ca2+ concentration [1]. Recently, we identified cAMP as a novel early signaling molecule in primary cilia-dependent mechanotransduction of fluid flow in osteocytes. Specifically, we show that MLO-Y4 osteocyte-like cells respond to oscillatory flow with a rapid decrease in intracellular levels of cAMP that is dependent on the primary cilium [2]. Adenylyl cyclase 6 (AC6) is an enzyme responsible for the synthesis of cAMP from ATP. We found that AC 6 localizes to the primary cilium of bone cells (Fig. 1). In this study, our goal was to determine whether AC6 mediates the primary cilia-dependent, flow-induced decrease in cAMP.