C11ORF74 interacts with the IFT-A complex and participates in ciliary BBSome localization.

Cilia are organelles that serve as cellular antennae. Intraflagellar transport particles containing the IFT-A and IFT-B complexes mediate bidirectional trafficking of ciliary proteins. Particularly, in concert with the BBSome complex, IFT particles play an essential role in trafficking of ciliary G-protein-coupled receptors (GPCRs). Therefore, proteins interacting with the IFT components are potential regulators of ciliary protein trafficking. We here revealed that an uncharacterized protein, C11ORF74, interacts with the IFT-A complex via the IFT122 subunit and is accumulated at the distal tip in the absence of an IFT-A subunit IFT139, suggesting that at least a fraction of C11ORF74 molecules can be transported towards the ciliary tip by associating with the IFT-A complex, although its majority might be out of cilia at steady state. In C11ORF74-knockout (KO) cells, the BBSome components cannot enter cilia. However, trafficking of Smoothened or GPR161, both of which are ciliary GPCRs involved in Hedgehog signalling and undergo BBSome-dependent trafficking, was not affected in the absence of C11ORF74. In addition, C11orf74/B230118H07Rik- KO mice demonstrated no obvious anatomical abnormalities associated with ciliary dysfunctions. Given that C11ORF74 is conserved across vertebrates, but not found in other ciliated organisms, such as nematodes and Chlamydomonas, it might play limited roles involving cilia.