title: Rab8a and Rab8b are essential for several apical transport pathways but insufficient for ciliogenesis.
abstract: The small GTP-binding protein Rab8 is known to play an essential role in intracellular transport and cilia formation. We have previously demonstrated that Rab8a is required for localising apical markers in various organisms. Rab8a has a closely related isoform, Rab8b. To determine whether Rab8b can compensate for Rab8a, we generated Rab8b-knockout mice. Although the Rab8b-knockout mice did not display an overt phenotype, Rab8a and Rab8b double-knockout mice exhibited mislocalisation of apical markers and died earlier than Rab8a-knockout mice. The apical markers accumulated in three intracellular patterns in the double-knockout mice. However, the localisation of basolateral and/or dendritic markers of the double-knockout mice seemed normal. The morphology and the length of various primary and/or motile cilia, and the frequency of ciliated cells appeared to be identical in control and double-knockout mice. However, an additional knockdown of Rab10 in double-knockout cells greatly reduced the percentage of ciliated cells. Our results highlight the compensatory effect of Rab8a and Rab8b in apical transport, and the complexity of the apical transport process. In addition, neither Rab8a nor Rab8b are required for basolateral and/or dendritic transport. However, simultaneous loss of Rab8a and Rab8b has little effect on ciliogenesis, whereas additional loss of Rab10 greatly affects ciliogenesis.
authors.affiliation: Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8512, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Iwano
authors.forename: Masataka
authors.initials: M
authors.lastname: Kunii
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsuda
authors.forename: Rumiko
authors.initials: R
authors.lastname: Mizuguchi
authors.forename: Yongwook
authors.initials: Y
authors.lastname: Jung
authors.forename: Haruo
authors.initials: H
authors.lastname: Hagiwara
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoshihara
authors.forename: Michisuke
authors.initials: M
authors.lastname: Yuzaki
authors.forename: Reiko
authors.initials: R
authors.lastname: Harada
authors.forename: Akihiro
authors.initials: A
authors.lastname: Harada
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001284:Atrophy; D001692:Biological Transport; D015415:Biomarkers / Q000378:metabolism; D016764:Cell Polarity; D002478:Cells, Cultured; D002923:Cilia / Q000378:metabolism* / Q000648:ultrastructure; D007421:Intestine, Small / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D008871:Microvilli / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D038081:Organogenesis; D010641:Phenotype; D020691:rab GTP-Binding Proteins / Q000172:deficiency / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C546061:Rab8a protein, mouse; C520736:Rab10 protein, mouse; C576245:Rab8b protein, mouse; D020691:rab GTP-Binding Proteins
keywords: Apical membrane; Cell polarity; Cilia; Knockout mouse; Rab8a; Rab8b