Rab8a and Rab8b are essential for multiple apical transport pathways but insufficient for ciliogenesis

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. Though the Rab8b-knockout mice did not display an overt phenotype, the Rab8a and Rab8b double-knockout mice exhibited mislocalisation of apical markers and died earlier than the Rab8a-knockout mice. The apical markers accumulated in three intracellular patterns in the double-knockout mice. However, the localisations of basolateral/dendritic markers of the double-knockout mice were apparently normal. The morphology and the lengths of various primary/motile cilia and the frequency of ciliated cells appeared to be identical between the control and double-knockout mice. However, an additional knockdown of Rab10 in the 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/dendritic transport. In the meantime, the simultaneous loss of Rab8a and Rab8b has little effect on ciliogenesis, while the additional loss of Rab10 greatly affects ciliogenesis. (203 words)