RRC ID 48554
著者 Aizawa M, Fukuda M.
タイトル Small GTPase Rab2B and Its Specific Binding Protein Golgi-associated Rab2B Interactor-like 4 (GARI-L4) Regulate Golgi Morphology.
ジャーナル J Biol Chem
Abstract Rab small GTPases are crucial regulators of the membrane traffic that maintains organelle identity and morphology. Several Rab isoforms are present in the Golgi, and it has been suggested that they regulate the compacted morphology of the Golgi in mammalian cells. However, the functional relationships among the Golgi-resident Rabs, e.g. whether they are functionally redundant or different, are poorly understood. In this study, we used specific siRNAs to perform genome-wide screening for human Rabs that are involved in Golgi morphology in HeLa-S3 cells. The results showed that knockdown of any one of the six Rab isoforms (Rab1A/1B/2A/2B/6B/8A) induced fragmentation of the Golgi in HeLa-S3 cells and that its phenotype was rescued by re-expression of their respective siRNA-resistant construct. We then performed systematic knockdown-rescue experiments in relation to each of the six Rabs. Interestingly, with the exception of the Rab8A knockdown, the Golgi fragmentation phenotype induced by knockdown of a single Rab isoform, e.g. Rab2B, was efficiently rescued by re-expression of its siRNA-resistant Rab alone, not by any of the other five Rabs, e.g. Rab2A, which is highly homologous to Rab2B, indicating that these Rab isoforms non-redundantly regulate Golgi morphology possibly through interaction with isoform-specific effector molecules. In addition, we identified Golgi-associated Rab2B interactor-like 4 (GARI-L4) as a novel Golgi-resident Rab2B-specific binding protein whose knockdown also induced fragmentation of the Golgi. Our findings suggest that the compacted Golgi morphology of mammalian cells is finely tuned by multiple sets of Rab (or Rab-effector complexes) that for the most part function independently.
巻・号 290(36)
ページ 22250-61
公開日 2015-9-4
DOI 10.1074/jbc.M115.669242
PII S0021-9258(20)44882-3
PMID 26209634
PMC PMC4571976
MeSH Animals COS Cells Carrier Proteins / genetics Carrier Proteins / metabolism* Chlorocebus aethiops Golgi Apparatus / metabolism* HeLa Cells Humans Immunoblotting Microscopy, Fluorescence Protein Binding Protein Isoforms / genetics Protein Isoforms / metabolism RNA Interference rab2 GTP-Binding Protein / genetics rab2 GTP-Binding Protein / metabolism*
IF 4.238
引用数 21
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
遺伝子材料 pEF-BOS FLAG-mouse Rab2B (RDB14676) pEF-T7-mouse GARI-L4 (RDB15396) pEGFP-C1-Rab6D (RDB17252) pEGFP-C1-Rab40AL (RDB17288).
ヒト・動物細胞 HeLa.S3(RCB0191)