{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DNAI4 is one of the genes encoding an axonemal dynein intermediate chain that is essential for the proper assembly, stability, and regulation of the inner dynein arms in motile cilia and flagella. Although not mentioned by name in these abstracts, several of the studies provide context for the role of dynein components in ciliary function. For example, one study identified a co‐chaperone (ZMYND10) that confers specificity to the FKBP8–HSP90 chaperone complex in the folding and assembly of axonemal dynein heavy chains; defects in this process are known to impair dynein motor stability and lead to ciliary dyskinesia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " \n Similarly, other work (though partially truncated) indicates that mutations in genes affecting the axonemal dynein pre‐assembly factors can cause primary ciliary dyskinesia, further underscoring the critical role dynein intermediate chain proteins play in achieving effective ciliary beating."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, experimental studies in model organisms have shown that intermediate chain components analogous to DNAI4 are crucial for modulating the dynein “I1” complex that governs flagellar waveform and microtubule sliding velocities. For instance, genetic disruption of the IC138 subcomplex leads to abnormal flagellar beating and reduced motility, a phenotype that implicates intermediate chains in the regulation of dynein motor activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies support the concept that DNAI4—like other dynein intermediate chain proteins—serves a structural and regulatory function in the formation and proper operation of the inner dynein arms. Disruption of DNAI4 function can, therefore, be expected to impair dynein pre‐assembly and ciliary/flagellar motility, leading to conditions such as primary ciliary dyskinesia.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Girish R Mali, Patricia L Yeyati, Seiya Mizuno, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZMYND10 functions in a chaperone relay during axonemal dynein assembly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.34389"}], "href": "https://doi.org/10.7554/eLife.34389"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29916806"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29916806"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Petra Zur Lage, Fay G Newton, Andrew P Jarman "}, {"type": "b", "children": [{"type": "t", "text": "Survey of the Ciliary Motility Machinery of "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "Drosophila"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Sperm and Ciliated Mechanosensory Neurons Reveals Unexpected Cell-Type Specific Variations: A Model for Motile Ciliopathies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fgene.2019.00024"}], "href": "https://doi.org/10.3389/fgene.2019.00024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30774648"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30774648"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kristyn E VanderWaal, Ryosuke Yamamoto, Ken-ichi Wakabayashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "bop5 Mutations reveal new roles for the IC138 phosphoprotein in the regulation of flagellar motility and asymmetric waveforms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E11-03-0270"}], "href": "https://doi.org/10.1091/mbc.E11-03-0270"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21697502"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21697502"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Corinne S Wilson, Alex J Chang, Rebecca Greene, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of Inner Arm Protein IC138 in Trypanosoma brucei Causes Defective Motility and Flagellar Detachment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0139579"}], "href": "https://doi.org/10.1371/journal.pone.0139579"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26555902"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26555902"}]}]}]}