RABL2 interacts with the intraflagellar transport-B complex and CEP19 and participates in ciliary assembly.
RABL2 interacts with the intraflagellar transport-B complex and CEP19 and participates in ciliary assembly.
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DOI：
10.1091/mbc.e17-01-0017
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发表时间：
2017-06-15
影响因子：
3.3
通讯作者：
Nakayama K
中科院分区：
文献类型：
--
作者：
Nishijima Y;Hagiya Y;Kubo T;Takei R;Katoh Y;Nakayama K
RABL 2与鞭毛内转运蛋白B（IFT-B）复合物和CEP 19以相互排斥的方式相互作用。在精子运动缺陷小鼠中发现的RABL 2点突变废除了其与IFT-B的结合，但不与CEP 19结合。RABL 2缺陷型衣原体菌株表现出非鞭毛型，表明RABL 2在纤毛装配中起着至关重要的作用。定位于基体和中心体的蛋白质在纤毛组装和功能中起着至关重要的作用。虽然RABL 2和CEP 19在纤毛生物中是保守的，并且与纤毛/鞭毛功能有关，但它们的作用知之甚少。在这里，我们表明，RABL 2与CEP 19相互作用，并招募到母亲中心粒和基体中的CEP 19依赖的方式和CEP 19招募到中心粒可能通过其结合到中心体蛋白FGFR 1 OP。RABL 2基因在莱茵衣藻中的破坏导致无鞭毛表型，表明RABL 2在纤毛/鞭毛组装中的关键作用。我们还表明，RABL 2相互作用，在其GTP结合状态下，与鞭毛内运输（IFT）-B复合物通过IFFT 74-IFFT 81异源二聚体和相互作用被破坏的突变中发现的雄性不育小鼠（Mot小鼠）与精子鞭毛运动缺陷。有趣的是，RABL 2以相互排斥的方式结合CEP 19和IFT 74-IFT 81异二聚体。此外，人细胞中GDP锁定或Mot型RABL 2突变体的外源表达导致纤毛组装的轻度缺陷。这些结果表明，定位于基底体的RABL 2通过与IFT-B复合物的相互作用在纤毛/鞭毛组装中发挥关键作用。
RABL2 interacts with the intraflagellar transport-B (IFT-B) complex and CEP19 in a mutually exclusive manner. A point mutation of RABL2 found in sperm motility–defective mice abolishes its binding to IFT-B but not to CEP19. A RABL2-defective Chlamydomonas strain exhibits a nonflagellated phenotype, suggesting a crucial role of RABL2 in ciliary assembly. Proteins localized to the basal body and the centrosome play crucial roles in ciliary assembly and function. Although RABL2 and CEP19 are conserved in ciliated organisms and have been implicated in ciliary/flagellar functions, their roles are poorly understood. Here we show that RABL2 interacts with CEP19 and is recruited to the mother centriole and basal body in a CEP19-dependent manner and that CEP19 is recruited to the centriole probably via its binding to the centrosomal protein FGFR1OP. Disruption of the RABL2 gene in Chlamydomonas reinhardtii results in the nonflagellated phenotype, suggesting a crucial role of RABL2 in ciliary/flagellar assembly. We also show that RABL2 interacts, in its GTP-bound state, with the intraflagellar transport (IFT)-B complex via the IFT74–IFT81 heterodimer and that the interaction is disrupted by a mutation found in male infertile mice (Mot mice) with a sperm flagella motility defect. Intriguingly, RABL2 binds to CEP19 and the IFT74–IFT81 heterodimer in a mutually exclusive manner. Furthermore, exogenous expression of the GDP-locked or Mot-type RABL2 mutant in human cells results in mild defects in ciliary assembly. These results indicate that RABL2 localized to the basal body plays crucial roles in ciliary/flagellar assembly via its interaction with the IFT-B complex.