Pratt Metta B, Titlow Joshua S, Davis Ilan, Barker Amy R, Dawe Helen R, Raff Jordan W, Roque Helio
The Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
J Cell Sci. 2016 Oct 15;129(20):3732-3743. doi: 10.1242/jcs.194621. Epub 2016 Aug 30.
Cilia are conserved organelles that have important motility, sensory and signalling roles. The transition zone (TZ) at the base of the cilium is crucial for cilia function, and defects in several TZ proteins are associated with human congenital ciliopathies such as nephronophthisis (NPHP) and Meckel-Gruber syndrome (MKS). In several species, MKS and NPHP proteins form separate complexes that cooperate with Cep290 to assemble the TZ, but flies seem to lack core components of the NPHP module. We show that MKS proteins in flies are spatially separated from Cep290 at the TZ, and that flies mutant for individual MKS genes fail to recruit other MKS proteins to the TZ, whereas Cep290 seems to be recruited normally. Although there are abnormalities in microtubule and membrane organisation in developing MKS mutant cilia, these defects are less apparent in adults, where sensory cilia and sperm flagella seem to function quite normally. Thus, localising MKS proteins to the cilium or flagellum is not essential for viability or fertility in flies.
纤毛是保守的细胞器,具有重要的运动、传感和信号传导作用。纤毛基部的过渡区(TZ)对纤毛功能至关重要,几种TZ蛋白的缺陷与人类先天性纤毛病相关,如肾单位肾痨(NPHP)和梅克尔-格鲁伯综合征(MKS)。在几个物种中,MKS和NPHP蛋白形成单独的复合物,与Cep290协同组装TZ,但果蝇似乎缺乏NPHP模块的核心成分。我们发现果蝇中的MKS蛋白在TZ处与Cep290在空间上分离,单个MKS基因突变的果蝇无法将其他MKS蛋白招募到TZ,而Cep290似乎能正常被招募。尽管发育中的MKS突变纤毛的微管和膜组织存在异常,但这些缺陷在成体中不太明显,成体中的感觉纤毛和精子鞭毛似乎功能相当正常。因此,将MKS蛋白定位到纤毛或鞭毛对果蝇的生存能力或繁殖力并非必不可少。