Lee Eugene, Sivan-Loukianova Elena, Eberl Daniel F, Kernan Maurice J
Center for Developmental Genetics, Stony Brook University, Stony Brook, NY 11794, USA.
Curr Biol. 2008 Dec 23;18(24):1899-906. doi: 10.1016/j.cub.2008.11.020.
Conserved intraflagellar transport (IFT) particle proteins and IFT-associated motors are needed to assemble most eukaryotic cilia and flagella. Proteins in an IFT-A subcomplex are generally required for dynein-driven retrograde IFT, from the ciliary tip to the base. We describe novel structural and functional roles for IFT-A proteins in chordotonal organs, insect mechanosensory organs with cilia that are both sensory and motile.
The reduced mechanoreceptor potential A (rempA) locus of Drosophila encodes the IFT-A component IFT140. Chordotonal cilia are shortened in rempA mutants and an IFT-B protein accumulates in the mutant cilia, consistent with a defect in retrograde IFT. A functional REMPA-YFP fusion protein concentrates at the site of the ciliary dilation (CD), a highly structured axonemal inclusion of hitherto unknown composition and function. The CD is absent in rempA mutants, and REMPA-YFP is undetectable in the absence of another IFT-A protein, IFT122. In a mutant lacking the IFT dynein motor, the CD is disorganized and REMPA-YFP is mislocalized. A TRPV ion channel, required to generate sensory potentials and regulate ciliary motility, is normally localized in the cilia, proximal to the CD. This channel spreads into the distal part of the cilia in dynein mutants and is undetectable in rempA mutants.
IFT-A proteins are located at and required by the ciliary dilation, which separates chordotonal cilia into functionally distinct zones. A requirement for IFT140 in stable TRPV channel expression also suggests that IFT-A proteins may mediate preciliary transport of some membrane proteins.
大多数真核生物的纤毛和鞭毛组装需要保守的鞭毛内运输(IFT)颗粒蛋白和与IFT相关的马达蛋白。IFT-A亚复合物中的蛋白质通常是动力蛋白驱动的逆行IFT(从纤毛尖端到基部)所必需的。我们描述了IFT-A蛋白在弦音器官中的新结构和功能作用,弦音器官是昆虫的机械感觉器官,其纤毛兼具感觉和运动功能。
果蝇的机械感受器电位降低A(rempA)基因座编码IFT-A成分IFT140。弦音纤毛在rempA突变体中缩短,并且一种IFT-B蛋白在突变体纤毛中积累,这与逆行IFT缺陷一致。功能性REMPA-YFP融合蛋白集中在纤毛扩张部位(CD),这是一种结构高度复杂的轴丝内含物,其组成和功能迄今未知。CD在rempA突变体中不存在,并且在没有另一种IFT-A蛋白IFT122的情况下无法检测到REMPA-YFP。在缺乏IFT动力蛋白马达的突变体中,CD紊乱,REMPA-YFP定位错误。一种产生感觉电位和调节纤毛运动所需的TRPV离子通道通常定位在靠近CD的纤毛中。该通道在动力蛋白突变体中扩散到纤毛的远端部分,而在rempA突变体中无法检测到。
IFT-A蛋白位于纤毛扩张部位并为其所需,纤毛扩张部位将弦音纤毛分隔成功能不同的区域。对稳定的TRPV通道表达中IFT140的需求还表明,IFT-A蛋白可能介导某些膜蛋白的纤毛前运输。