Structural highlights
Disease
IF122_HUMAN Cranioectodermal dysplasia;Short rib-polydactyly syndrome, Beemer-Langer type. The disease is caused by variants affecting the gene represented in this entry.
Function
IF122_HUMAN As a component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is required in ciliogenesis and ciliary protein trafficking (PubMed:27932497, PubMed:29220510). Involved in cilia formation during neuronal patterning. Acts as a negative regulator of Shh signaling. Required to recruit TULP3 to primary cilia (By similarity).[UniProtKB:Q6NWV3][1] [2]
Publication Abstract from PubMed
Intraflagellar transport (IFT) trains are massive molecular machines that traffic proteins between cilia and the cell body. Each IFT train is a dynamic polymer of two large complexes (IFT-A and -B) and motor proteins, posing a formidable challenge to mechanistic understanding. Here, we reconstituted the complete human IFT-A complex and obtained its structure using cryo-EM. Combined with AlphaFold prediction and genome-editing studies, our results illuminate how IFT-A polymerizes, interacts with IFT-B, and uses an array of beta-propeller and TPR domains to create "carriages" of the IFT train that engage TULP adaptor proteins. We show that IFT-Aâ
TULP carriages are essential for cilia localization of diverse membrane proteins, as well as ICK-the key kinase regulating IFT train turnaround. These data establish a structural link between IFT-A's distinct functions, provide a blueprint for IFT-A in the train, and shed light on how IFT evolved from a proto-coatomer ancestor.
IFT-A structure reveals carriages for membrane protein transport into cilia.,Hesketh SJ, Mukhopadhyay AG, Nakamura D, Toropova K, Roberts AJ Cell. 2022 Dec 22;185(26):4971-4985.e16. doi: 10.1016/j.cell.2022.11.010. Epub , 2022 Dec 2. PMID:36462505[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hirano T, Katoh Y, Nakayama K. Intraflagellar transport-A complex mediates ciliary entry and retrograde trafficking of ciliary G protein-coupled receptors. Mol Biol Cell. 2017 Feb 1;28(3):429-439. PMID:27932497 doi:10.1091/mbc.E16-11-0813
- ↑ Takahara M, Katoh Y, Nakamura K, Hirano T, Sugawa M, Tsurumi Y, Nakayama K. Ciliopathy-associated mutations of IFT122 impair ciliary protein trafficking but not ciliogenesis. Hum Mol Genet. 2018 Feb 1;27(3):516-528. PMID:29220510 doi:10.1093/hmg/ddx421
- ↑ Hesketh SJ, Mukhopadhyay AG, Nakamura D, Toropova K, Roberts AJ. IFT-A structure reveals carriages for membrane protein transport into cilia. Cell. 2022 Nov 30:S0092-8674(22)01422-2. doi: 10.1016/j.cell.2022.11.010. PMID:36462505 doi:http://dx.doi.org/10.1016/j.cell.2022.11.010
