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Coordinate roles for Itg 8 and Pcdh 15 in the regulation of cilia biogenesis in sensory cells

The organism’s perception of its surroundings depends on sensory systems and the highly specialized cilia present in the neurosensory cells. Here, we described the existence of an integrin alpha 8 (Itga8)/protocadherin-15a (Pcdh15a) ciliary complex in neuromast hair cells. Depletion of the complex via down-regulation or loss of function mutations leads to a dysregulation of cilia biogenesis and endocytosis. At the molecular level, removal of the complex blocks the access of Rab8a into the cilia as well as normal recruitment of ciliary cargo by centriolar satellites. These defects can be reversed by the introduction of a constitutively active form of Rhoa, suggesting that Itga8/Pcdh15a complex mediates its effect through the activation of this small-GTPase and probably by the regulation of actin cytoskeleton dynamics. Our data points to a novel mechanism involved in the regulation of sensory cilia development, with the corresponding implications for normal sensory function. Jo ur na l o f C el l S ci en ce • A cc ep te d m an us cr ip t