Super-resolution architecture of mammalian centriole distal appendages reveals distinct blade and matrix functional components

Copyright © The Author(s) 2018. Distal appendages (DAPs) are nanoscale, pinwheel-like structures protruding from the distal end of the centriole that mediate membrane docking during ciliogenesis, marking the cilia base around the ciliary gate. Here we determine a super-resolved multiplex of 16 centriole-distal-end components. Surprisingly, rather than pinwheels, intact DAPs exhibit a cone-shaped architecture with components filling the space between each pinwheel blade, a new structural element we term the distal appendage matrix (DAM). Specifically, CEP83, CEP89, SCLT1, and CEP164 form the backbone of pinwheel blades, with CEP83 confined at the root and CEP164 extending to the tip near the membrane-docking site. By contrast, FBF1 marks the distal end of the DAM near the ciliary membrane. Strikingly, unlike CEP164, which is essential for ciliogenesis, FBF1 is required for ciliary gating of transmembrane proteins, revealing DAPs as an essential component of the ciliary gate. Our findings redefine both the structure and function of DAPs.Ministry of Science and Technology, Taiwan (Grant Number 103-2112-M-001-039-MY3); Academia Sinica Career Development Award, Academia Sinica Nano Program; University of Alabama at Birmingham (UAB) Hepato/Renal Fibrocystic Diseases Core Center (HRFDCC) Pilot Award (NIH 5P30DK074038-09); NIH grant GM088253, American Cancer Society grant RSG-14-153-01-CCG; Geoffrey Beene Cancer Research Center grant

Quantitative fractographic analysis of impact fracture surfaces of steel R73

Macroscopic images offracture surfaces of Charpy test specimens of steel R73 were studied, where bright spots in images represent cleavage facets or ductile dimples, respectively, both in special orientations. Within image analysis, they may be taken for the most significant textural element. Being the brightest patches in the image, they can be extracted by thresholding. Their counts and area distribution are closely related to temperature and impact energy.Выполнены исследования макроизображений поверхностей разрушений образцов Шарпи из стали R73. При специальных условиях ориентации поверхностей разрушения видны яркие участки на изображениях, соответствующие граням скола или ямкам вязкого разрушения. Эти участки могут быть использованы в качестве основного элемента текстуры для обработки изображения. Поскольку эти участки на изображениях являются наиболее яркими, их можно отсеять путем настройки порогового уровня освещенности. Результаты расчета относительной доли их площади тесно коррелируют с температурой и энергией ударного разрушения

DEPDC1/LET-99 participates in an evolutionarily conserved pathway for anti-tubulin drug-induced apoptosis

Microtubule-targeting chemotherapeutics induce apoptosis in cancer cells by promoting the phosphorylation and degradation of the anti-apoptotic BCL-2 family member MCL1. The signalling cascade linking microtubule disruption to MCL1 degradation remains however to be defined. Here, we establish an in vivo screening strategy in Caenorhabditis elegans to uncover genes involved in chemotherapy-induced apoptosis. Using an RNAi-based screen, we identify three genes required for vincristine-induced apoptosis. We show that the DEP domain protein LET-99 acts upstream of the heterotrimeric G protein alpha subunit GPA-11 to control activation of the stress kinase JNK-1. The human homologue of LET-99, DEPDC1, similarly regulates vincristine-induced cell death by promoting JNK-dependent degradation of the BCL-2 family protein MCL1. Collectively, these data uncover an evolutionarily conserved mediator of anti-tubulin drug-induced apoptosis and suggest that DEPDC1 levels could be an additional determinant for therapy response upstream of MCL1