Abstract
Cilia are highly conserved microtubule-based structures that perform a variety of sensory and motility functions during development and adult homeostasis. In humans, defects specifically affecting motile cilia lead to chronic airway infections, infertility and laterality defects in the genetically heterogeneous disorder Primary Ciliary Dyskinesia (PCD). Using the comparatively simple Drosophila system, in which mechanosensory neurons possess modified motile cilia, we employed a recently elucidated cilia transcriptional RFX-FOX code to identify novel PCD candidate genes. Here, we report characterization of CG31320/HEATR2, which plays a conserved critical role in forming the axonemal dynein arms required for ciliary motility in both flies and humans. Inner and outer arm dyneins are absent from axonemes of CG31320 mutant flies and from PCD individuals with a novel splice-acceptor HEATR2 mutation. Functional conservation of closely arranged RFX-FOX binding sites upstream of HEATR2 orthologues may drive higher cytoplasmic expression of HEATR2 during early motile ciliogenesis. Immunoprecipitation reveals HEATR2 interacts with DNAI2, but not HSP70 or HSP90, distinguishing it from the client/chaperone functions described for other cytoplasmic proteins required for dynein arm assembly such as DNAAF1-4. These data implicate CG31320/HEATR2 in a growing intracellular pre-assembly and transport network that is necessary to deliver functional dynein machinery to the ciliary compartment for integration into the motile axoneme.
Highlights
Cilia and flagella are small microtubule-based projections on the cell surface, where they perform diverse sensory, and in some cases motility functions
Ciliary motility is defective in the inherited disease, Primary Ciliary Dyskinesia (PCD)
We have used the comparatively simple fruit fly, which has motile cilia on only a handful of touch-sensitive sensory cells, to identify genes involved in ciliary motility and which are candidate genes for causing PCD
Summary
Cilia and flagella are small microtubule-based projections on the cell surface, where they perform diverse sensory, and in some cases motility functions These highly conserved organelles are found across species from protozoa to mammals, and are believed to have evolved from flagellar structures found in the last eukaryotic common ancestor (LECA) [1]. Axonemes of motile cilia, which usually have an additional central pair of singlet microtubules in a ‘‘9+2’’ arrangement, possess inner (IDA) and outer dynein arms (ODA) attached to the peripheral outer doublet A microtubule. These orchestrate the ATP-dependent sliding of the doublets relative to each other, enabling motility.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
