Hearing in Drosophila Requires TilB, a Conserved Protein Associated With Ciliary Motility
Hearing in Drosophila Requires TilB, a Conserved Protein Associated With Ciliary Motility
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DOI：
10.1534/genetics.110.114009
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发表时间：
2010-05-01
期刊：
影响因子：
3.3
通讯作者：
Eberl, Daniel F.
中科院分区：
文献类型：
--
作者：
Kavlie, Ryan G.;Kernan, Maurice J.;Eberl, Daniel F.
纤毛存在于最早的真核生物祖先中，并且是从细胞运动和细胞外液推进到感觉生理学的许多生物过程的基础。我们研究了触觉不敏感幼虫B（til B）基因对果蝇纤毛功能的贡献。tilB的突变体表现出精子鞭毛和调节听力和幼虫触摸敏感性的弦音器官的纤毛树枝的功能障碍。突变的精子轴丝以及约翰斯顿器官（果蝇的听觉器官）的感觉神经元树突缺乏动力蛋白臂。通过缺陷定位和候选基因测序，我们确定了注释基因CG 14620中的tilB突变。基因组CG 14620转基因挽救了tilB突变体的耳聋和雄性不育。TilB是一种395个氨基酸的蛋白质，在残基16-164处具有保守的N-末端富含亮氨酸的重复区，并且在残基171-191处具有卷曲螺旋结构域。驱动荧光标记的TilB蛋白质的TilB-Gal 4转基因在胚胎弦音器官、约翰斯顿器官和精子鞭毛中激发细胞质表达。TilB似乎不影响微管蛋白多聚谷氨酰化或多聚甘氨酰化。tilB的表型和表达表明在纤毛的建设或维护功能，但不是在鞭毛内运输。这也与tilB同源物与编码轴丝动力蛋白臂组分的基因的存在的系统发育关联一致。进一步阐明tilB的功能机制将提供更好的理解纤毛功能，并将有助于了解纤毛疾病。
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.