Cilium-generated signaling: a cellular GPS?

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Abstract
The discovery of the importance of proteins localized to cilia and basal bodies has provided novel insights into the pathogenesis of various human disorders including cystic kidney disease. The physiological role of cilium-generated signaling in most tissues including the kidney has remained elusive, however. This review focuses on the most recent advance in understanding a role for signaling through cilia for kidney biology. Recent work has tied the function of several developmental master regulators to cilium-generated signaling in vertebrates. Hedgehog signaling requires ciliary proteins and loss of targeting of its receptors and effectors to cilia abrogates Hedgehog function. Moreover, the ciliary protein inversin has been shown to act as a molecular switch for the regulation of Wnt signaling cascades. Together with recent data on a function of cilia and basal body proteins in planar cell polarity in mice, a novel concept and testable hypothesis for the function of cilia in vertebrates is emerging: cilia may act as a cellular positioning device to allow subcellular asymmetry and polarization of the cells within the plane of the epithelium to develop and maintain regular arrays of cells such as kidney tubes.

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