{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n IFT46 is a highly conserved core component of the IFT‐B complex that plays critical roles in cilia and flagella assembly, maintenance, and function. It forms part of a subcomplex together with other IFT‐B proteins (such as IFT88 and IFT52) that enables the pre‐assembly and subsequent intraflagellar transport of key axonemal cargos—including outer dynein arms—into the ciliary compartment."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n IFT46 also mediates specific protein–protein interactions that are essential for proper cargo delivery and ciliary signaling. For example, it forms a dimer together with IFT56 that binds the small GTPase ARL13B and contributes to the ciliary targeting of regulatory proteins, while its association with the kinesin motor KIF17 helps facilitate motor entry into cilia."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Functional studies in various model systems have shown that disruption of IFT46 results in defects ranging from abnormal dynein arm import to gross ciliary malformation. Loss of IFT46 in unicellular models such as Paramecium leads to severe ciliary growth defects with decreased cilia number and length, while in Chlamydomonas, its role in loading dynein arms is essential for flagellar assembly."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In vertebrate systems, IFT46 is critical for proper ciliogenesis and developmental processes. Its deficiency not only disrupts ciliary architecture but also impacts neurogenesis and craniofacial development, highlighting its broader significance in tissue patterning."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Moreover, sequence elements within IFT46 contribute to its targeted localization at basal bodies, and altered expression of IFT46 has been linked in some studies to cellular processes relevant to disease, such as changes in macrophage composition in paclitaxel‐treated breast cancer cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings establish IFT46 as a pivotal mediator in ciliary protein trafficking that integrates the assembly of ciliary structures with the delivery of functional components critical for cell motility and signal transduction.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ben F Lucker, Mark S Miller, Slawomir A Dziedzic, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Direct interactions of intraflagellar transport complex B proteins IFT88, IFT52, and IFT46."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.106997"}], "href": "https://doi.org/10.1074/jbc.M110.106997"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20435895"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20435895"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jiaolong Wang, Michael Taschner, Narcis A Petriman, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Ciliary entry of KIF17 is dependent on its binding to the IFT-B complex via IFT46-IFT56 as well as on its nuclear localization signal."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E16-09-0648"}], "href": "https://doi.org/10.1091/mbc.E16-09-0648"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28077622"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28077622"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Sebiha Cevik, Anna A W M Sanders, Erwin Van Wijk, et al. 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