A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2019; you can also visit <a rel="external noopener" href="http://pdfs.semanticscholar.org/1283/79bace69d1301f2c6aafa4ec3ab59545693e.pdf">the original URL</a>. The file type is <code>application/pdf</code>.
<i title="Proceedings of the National Academy of Sciences">
<a target="_blank" rel="noopener" href="https://fatcat.wiki/container/nvtuoas5pbdsllkntnhizy4f4q" style="color: black;">Proceedings of the National Academy of Sciences of the United States of America</a>
The intraflagellar transport (IFT) complex is an integral component of the cilium, a quintessential organelle of the eukaryotic cell. The IFT system consists of three subcomplexes [i.e., intraflagellar transport (IFT)-A, IFT-B, and the BBSome], which together transport proteins and other molecules along the cilium. IFT dysfunction results in diseases collectively called ciliopathies. It has been proposed that the IFT complexes originated from vesicle coats similar to coat protein complex (COP)<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1073/pnas.1221011110">doi:10.1073/pnas.1221011110</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/23569277">pmid:23569277</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC3637775/">pmcid:PMC3637775</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/gg73egkvlbgdpjum5yv7vowe2u">fatcat:gg73egkvlbgdpjum5yv7vowe2u</a> </span>
more »... , COPII, and clathrin. Here we provide phylogenetic evidence for common ancestry of IFT subunits and α, β′, and e subunits of COPI, and trace the origins of the IFT-A, IFT-B, and the BBSome subcomplexes. We find that IFT-A and the BBSome likely arose from an IFT-B-like complex by intracomplex subunit duplication. The distribution of IFT proteins across eukaryotes identifies the BBSome as a frequently lost, modular component of the IFT. Significantly, loss of the BBSome from a taxon is a frequent precursor to complete cilium loss in related taxa. Given the inferred late origin of the BBSome in cilium evolution and its frequent loss, the IFT complex behaves as a "last-in, first-out" system. The protocoatomer origin of the IFT complex corroborates involvement of IFT components in vesicle transport. Expansion of IFT subunits by duplication and their subsequent independent loss supports the idea of modularity and structural independence of the IFT subcomplexes. complex modularity | molecular evolution T he eukaryotic cilium or flagellum is a structure protruding from the cell into the environment. The cilium provides motility by a controlled whip-like or rotational beating. Construction and maintenance of the cilium, together with additional signaling functions, depend on the process of intraflagellar transport (IFT). IFT provides active, bidirectional transport of proteins and other molecules along the length of the cilium, delivering structural components and other factors in the organelle. IFT dysfunction results in the inability of the cilium to maintain a normal structure and failure of signaling and sensory pathways, causing complex system-wide disorders and syndromes (1). IFT is mediated by a large cohort of evolutionarily conserved subunits, which can be grouped by biochemical and genetic criteria into three subcomplexes: IFT-A, IFT-B, and BBSome. Broadly, mutations in any subunit of each of these complexes phenocopy each other, indicating close cooperativity and a requirement for complete holocomplexes for functional IFT. Significantly, six IFT complex subunits (WDR19, WDR35, IFT140, IFT122, IFT172, and IFT80) have predicted secondary structure elements and folds similar to those present in multiple subunits of vesicle coat complexes and the nuclear pore complex (NPC) (2-4). Their N-terminal region contains WD40 repeats, likely forming two β-propeller folds, whereas their C-terminal region contains tetratricopeptide repeats (TPR), likely forming an α-solenoid-like fold. The IFT system has been shown to be homologous to the protocoatomer family of complexes, which includes coat protein complex (COP) I, COPII, clathrin/adaptin complex, and the NPC scaffold (2-4). This classification was based on sequence similarity of IFT subunits to the COPI-α and -β′ subunits, further supported by secondary structure predictions. However, a full phylogenetic reconstruction and structural analysis of the IFT complex has not been performed. Such an analysis is necessary because the abundance of the WD40 and TPR domains in noncoatomer subunit proteins requires more than sequence similarity to establish a close phylogenetic relationship. Here, we have reconstructed the evolution of the IFT complex in detail, and provide phylogenetic evidence that the IFT complex is indeed a sister structure to COPI. Analysis of the presence of the individual subcomplexes in currently living eukaryotes shows that the presence and inferred order of the loss of subcomplexes mirrors their origin-the IFT subcomplex that was added latest in evolution is the first to be lost.
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20190219001147/http://pdfs.semanticscholar.org/1283/79bace69d1301f2c6aafa4ec3ab59545693e.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/12/83/128379bace69d1301f2c6aafa4ec3ab59545693e.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1073/pnas.1221011110"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> Publisher / doi.org </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637775" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>