Hearing in Drosophila Requires TilB, a Conserved Protein Associated With Ciliary Motility

Abstract

Cilia were present in the earliest eukaryotic ancestor and underlie many biological processes ranging from cell motility and propulsion of extracellular fluids to sensory physiology. We investigated the contribution of the touch insensitive larva B (tilB) gene to cilia function in Drosophila melanogaster. Mutants of tilB exhibit dysfunction in sperm flagella and ciliated dendrites of chordotonal organs that mediate hearing and larval touch sensitivity. Mutant sperm axonemes as well as sensory neuron dendrites of Johnston's organ, the fly's auditory organ, lack dynein arms. Through deficiency mapping and sequencing candidate genes, we identified tilB mutations in the annotated gene CG14620. A genomic CG14620 transgene rescued deafness and male sterility of tilB mutants. TilB is a 395-amino-acid protein with a conserved N-terminal leucine-rich repeat region at residues 16-164 and a coiled-coil domain at residues 171-191. A tilB-Gal4 transgene driving fluorescently tagged TilB proteins elicits cytoplasmic expression in embryonic chordotonal organs, in Johnston's organ, and in sperm flagella. TilB does not appear to affect tubulin polyglutamylation or polyglycylation. The phenotypes and expression of tilB indicate function in cilia construction or maintenance, but not in intraflagellar transport. This is also consistent with phylogenetic association of tilB homologs with presence of genes encoding axonemal dynein arm components. Further elucidation of tilB functional mechanisms will provide greater understanding of cilia function and will facilitate understanding ciliary diseases.

LRRC6 Mutation Causes Primary Ciliary Dyskinesia with Dynein Arm Defects

“…D. melanogaster tilB mutants have defective sperm flagella motility and dysfunctional ciliated dendrites of the chordotonal organs. Furthermore, these mutant sperm axoneme lacked dynein arms [46]. The LRRC6 orthologue, TbLRTP, of the T. brucei localizes to basal bodies and is critical for basal body duplication, flagellum assembly, and cytokinesis [47].…”

Dilatory is a Drosophila protein related to AZI1 (CEP131) that is located at the ciliary base and required for cilium formation

“…(O) Grossly malformed cilia in a dila mutant. which are thought to be required for the ciliary beat that occurs in response to mechanical stimulation and acts as a signal amplification mechanism (Göpfert and Robert, 2003; Kavlie et al, 2010). The disorganised axoneme patterns suggest that other axoneme-associated components are also missing, given that loss of dynein arms alone does not alter axoneme organisation (Kavlie et al, 2010). In contrast to the ciliary compartment, basal sections showed no obvious defects in the ciliary rootlet or basal bodies and their associated fibrous structures (Fig.…”

hemingwayis required for sperm flagella assembly and ciliary motility inDrosophila

“…This amplification is absent from flies carrying mutations in the gene touch insensitive larvae B ( tilB ), in which the axonemal dynein-like arms are lost (Kavlie et al ., 2010). …”