Precise regulation of centrosome position is critical for diverse processes including asymmetric cell division, neurogenesis, directed cell migration, and ciliogenesis. Primary cilia, present on the surface of most cell types in metazoans, are key mediators of diverse signaling pathways essential for embryonic development, sensory signal transduction, and adult tissue homeostasis. Cilia from all studied organisms share a conserved core organization comprised of a microtubule-based axoneme anchored by the basal body (BB) and surrounded by a specialized membrane. Primary cilium assembly is a multi-step process that relies on mother centriole-to-BB transition, BB migration and anchoring to membrane, establishment of the ‘ciliary gate’, and axoneme elongation from the BB via intraflagellar transport of ciliary components. Considerable progress has been made in identifying molecular components of distinct centrosomal and ciliary sub-compartments; however, the mechanisms regulating centrosome positioning during early steps of ciliogenesis are poorly understood. We find that the highly conserved signaling protein Girdin localizes to the BB in C. elegans sensory neurons and mammalian cells. Loss of grdn-1 function in C. elegans results in defective sensory cilia morphology, ultrastructure, and localization of BB, transition zone, and signaling proteins. Similarly, Girdin knockdown in mammalian RPE-1 cells leads to a complete loss of, or shortened cilia, and dissociation of the BB from the nucleus. These findings suggest a conserved function for Girdin in regulating centrosome positioning, and thereby ciliogenesis, in both C. elegans sensory neurons and mammalian cells. Mammalian Girdin has been previously implicated in regulating the actin cytoskeleton, and in coupling multiple classes of surface receptors to downstream signaling events in different contexts (e.g. cell migration, synaptic plasticity, and tumorigenesis). Therefore, Girdin is perfectly positioned to link extracellular cues to the cytoskeleton to ensure correct centrosome/BB positioning during primary cilia formation – a previously uncharacterized role for this protein in any species. We will present our ongoing efforts to further characterize the mechanism, by which Girdin regulates BB positioning and primary cilia biogenesis in C. elegans sensory neurons and mammalian cells.
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