The main force generators in eukaryotic cilia and flagella are axonemal outer dynein arms (ODAs). During ciliogenesis, these ~1.8-megadalton complexes are assembled in the cytoplasm and targeted to cilia by an unknown mechanism. Here, we used the ciliate to identify two factors (Q22YU3 and Q22MS1) that bind ODAs in the cytoplasm and are required for ODA delivery to cilia. Q22YU3, which we named Shulin, locked the ODA motor domains into a closed conformation and inhibited motor activity. Cryo-electron microscopy revealed how Shulin stabilized this compact form of ODAs by binding to the dynein tails. Our findings provide a molecular explanation for how newly assembled dyneins are packaged for delivery to the cilia.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116892 | PMC |
| http://dx.doi.org/10.1126/science.abe0526 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Cryo-electron tomography of eel sperm flagella reveals a molecular "minimum system" for motile cilia.
Mol Biol Cell
December 2024
Department of Cell Biology, University of Texas Southwestern Medical Center, Texas 75235, USA.
Cilia and flagella play a crucial role in the development and function of eukaryotes. The activity of thousands of dyneins is precisely regulated to generate flagellar motility. The complex proteome (600+ proteins) and architecture of the structural core of flagella, the axoneme, have made it challenging to dissect the functions of the different complexes, like the regulatory machinery.
View Article and Find Full Text PDFLoss of Downregulates Expression, Causing Cortical Development Disorders and Congenital Hydrocephalus.
Cells
November 2024
Department of Neurosurgery, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
is associated with primary ciliary dyskinesia in humans. -knockout (-/- mice develop acute hydrocephalus shortly after birth owing to impaired ciliary motility and cerebrospinal fluid (CSF) stagnation. In contrast to chronic adult-onset hydrocephalus observed in other models, this rapid ventricular enlargement indicates additional factors beyond CSF stagnation.
View Article and Find Full Text PDFCotranslational molecular condensation of cochaperones and assembly factors facilitates axonemal dynein biogenesis.
Proc Natl Acad Sci U S A
November 2024
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510.
Axonemal dynein, the macromolecular machine that powers ciliary motility, assembles in the cytosol with the help of dynein axonemal assembly factors (DNAAFs). These DNAAFs localize in cytosolic foci thought to form via liquid-liquid phase separation. However, the functional significance of DNAAF foci formation and how the production and assembly of multiple components are so efficiently coordinated, at such enormous scale, remain unclear.
View Article and Find Full Text PDFGlutamylation imbalance impairs the molecular architecture of the photoreceptor cilium.
EMBO J
December 2024
Department of Molecular and Cellular Biology, University of Geneva, Geneva, Switzerland.
Microtubules, composed of conserved α/β-tubulin dimers, undergo complex post-translational modifications (PTMs) that fine-tune their properties and interactions with other proteins. Cilia exhibit several tubulin PTMs, such as polyglutamylation, polyglycylation, detyrosination, and acetylation, with functions that are not fully understood. Mutations in AGBL5, which encodes the deglutamylating enzyme CCP5, have been linked to retinitis pigmentosa, suggesting that altered polyglutamylation may cause photoreceptor cell degeneration, though the underlying mechanisms are unclear.
View Article and Find Full Text PDFNovel variants in DNAH9 are present in two infertile patients with severe asthenospermia.
J Hum Genet
November 2024
Joint Laboratory of Reproductive Medicine, SCU-CUHK, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
Asthenospermia is a type of sperm that has malformed sperm with movement disorders that lead to male infertility. DNAH9 is a member of the dynein family and a central part of the outer dynein arm of cilia and flagella. DNAH9 gene defects are associated with primary ciliary dyskinesia and ultrastructural abnormalities in ciliary axial ultrastructure.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!