RRC ID 78526
Author Nishijima Y, Hagiya Y, Kubo T, Takei R, Katoh Y, Nakayama K.
Title RABL2 interacts with the intraflagellar transport-B complex and CEP19 and participates in ciliary assembly.
Journal Mol Biol Cell
Abstract 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.
Volume 28(12)
Pages 1652-1666
Published 2017-6-15
DOI 10.1091/mbc.E17-01-0017
PII mbc.E17-01-0017
PMID 28428259
PMC PMC5469608
MeSH Animals Basal Bodies / metabolism Biological Transport Cell Cycle Proteins / metabolism* Centrioles / metabolism Chlamydomonas reinhardtii / genetics Chlamydomonas reinhardtii / metabolism Cilia / metabolism* Flagella / metabolism HEK293 Cells Humans Infertility, Male / genetics Infertility, Male / metabolism Male Mice Phenotype Protein Binding Sperm Motility rab GTP-Binding Proteins / genetics rab GTP-Binding Proteins / metabolism*
DNA material pEGFP-C1-FOP(FGFR1OP) (RDB20236)