Ift22, also known as RabL5, is a subunit of the intraflagellar transport (IFT) complex crucial for cilia and flagella formation [1,2,3,4,5,6,7]. It is involved in the IFT pathway, which ferries flagellar precursors for assembly. The protein has sequence similarity to small GTPases and is part of the IFT-B1 subcomplex [1,2]. Ift22 is important for regulating ciliary functions, and its study has been facilitated by genetic models like C. elegans, Chlamydomonas reinhardtii, and zebrafish [2,3,5,6].

In Trypanosoma brucei, structure-based mutagenesis shows that the association of Ift22 with the IFT complex is essential for flagellum construction, though GTP-loading is not strictly required [1]. In Chlamydomonas reinhardtii, depletion of Ift22 leads to a smaller cellular pool of both IFT complex A and B, yet more IFT particle proteins accumulate in flagella, indicating its role in controlling IFT particle availability and flagellar partitioning [3]. Additionally, Ift22 regulates basal body targeting of the BBSome in Chlamydomonas reinhardtii. It binds and stabilizes BBS3, and when both are in GTP-bound states, they recruit the BBSome to the basal body for ciliary entry [2]. In zebrafish, knockdown of ift22 suppresses the bbs7-related retrograde transport delay, suggesting a role in intracellular transport [5].

In conclusion, Ift22 is essential for flagellum and cilia-related functions, such as IFT particle regulation and BBSome recruitment. Studies using model organisms have provided insights into its role in processes like flagellum assembly and intracellular transport, contributing to our understanding of ciliopathies and related diseases [1,2,3,5].

References:

1. Wachter, Stefanie, Jung, Jamin, Shafiq, Shahaan, Bastin, Philippe, Lorentzen, Esben. 2019. Binding of IFT22 to the intraflagellar transport complex is essential for flagellum assembly. In The EMBO journal, 38, . doi:10.15252/embj.2018101251. https://pubmed.ncbi.nlm.nih.gov/30940671/

2. Xue, Bin, Liu, Yan-Xia, Dong, Bin, Lechtreck, Karl F, Fan, Zhen-Chuan. 2020. Intraflagellar transport protein RABL5/IFT22 recruits the BBSome to the basal body through the GTPase ARL6/BBS3. In Proceedings of the National Academy of Sciences of the United States of America, 117, 2496-2505. doi:10.1073/pnas.1901665117. https://pubmed.ncbi.nlm.nih.gov/31953262/

3. Silva, David A, Huang, Xiaomeng, Behal, Robert H, Cole, Douglas G, Qin, Hongmin. 2012. The RABL5 homolog IFT22 regulates the cellular pool size and the amount of IFT particles partitioned to the flagellar compartment in Chlamydomonas reinhardtii. In Cytoskeleton (Hoboken, N.J.), 69, 33-48. doi:10.1002/cm.20546. https://pubmed.ncbi.nlm.nih.gov/22076686/

4. Lucker, Ben F, Miller, Mark S, Dziedzic, Slawomir A, Blackmarr, Philip T, Cole, Douglas G. 2010. Direct interactions of intraflagellar transport complex B proteins IFT88, IFT52, and IFT46. In The Journal of biological chemistry, 285, 21508-18. doi:10.1074/jbc.M110.106997. https://pubmed.ncbi.nlm.nih.gov/20435895/

5. Mei, Xue, Westfall, Trudi A, Zhang, Qihong, Bassuk, Alexander G, Slusarski, Diane C. 2014. Functional characterization of Prickle2 and BBS7 identify overlapping phenotypes yet distinct mechanisms. In Developmental biology, 392, 245-55. doi:10.1016/j.ydbio.2014.05.020. https://pubmed.ncbi.nlm.nih.gov/24938409/

6. Inglis, Peter N, Blacque, Oliver E, Leroux, Michel R. 2009. Functional genomics of intraflagellar transport-associated proteins in C. elegans. In Methods in cell biology, 93, 267-304. doi:10.1016/S0091-679X(08)93014-4. https://pubmed.ncbi.nlm.nih.gov/20409822/

7. Yang, Zhi, Zhang, Long, Zhang, Wenqing, Zhang, Zhengrui, Zhang, Zhifeng. 2024. Identification of the principal neuropeptide MIP and its action pathway in larval settlement of the echiuran worm Urechis unicinctus. In BMC genomics, 25, 337. doi:10.1186/s12864-024-10228-y. https://pubmed.ncbi.nlm.nih.gov/38641568/