IFT-A structure reveals carriages for membrane protein transport into cilia.

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 ß-propeller and TPR domains to create "carriages" of the IFT train that engage TULP adaptor proteins. We show that IFT-A⋅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.

The Prevalence and Characteristics of Diffuse Idiopathic Skeletal Hyperostosis (DISH): A Cross-Sectional Study of 1519 Japanese Individuals.

Background: Diffuse idiopathic skeletal hyperostosis (DISH) is a pathology characterized by enthesis ossification, but there have been few reports on epidemiological surveys. This report presents a cross-sectional survey of DISH from thoracic to sacral spine in patients at the tertiary emergency medical center. Methods: The patients were divided into DISH (+) group and DISH (−) group for a retrospective comparative study. The primary outcome measures were the frequency of DISH and the patient demographic data, the secondary outcome measures were the previous medical history (diabetes mellitus, cardiovascular disease), the extent of aortic calcification, the frequency of hyperostosis around the costovertebral joint and the mortality rate within 3 months of the initial examination. Results: This survey examined a total of 1519 patients. There were 265 cases (17.4%) in the DISH (+) group and 1254 cases in DISH (−) group. The prevalence of DISH was concentrated at the thoracolumbar junction, particularly at T9. The mean age, ratio of male and hyperostosis around the costovertebral joint were significantly higher in the DISH (+) group (p < 0.001), but there was no significant difference in other variables. Conclusions: The pathology of DISH might involve the effects of age-related changes or biomechanical effects.