Abstract:
:Motile ciliopathies are characterized by specific defects in cilia beating that result in chronic airway disease, subfertility, ectopic pregnancy, and hydrocephalus. While many patients harbor mutations in the dynein motors that drive cilia beating, the disease also results from mutations in so-called dynein axonemal assembly factors (DNAAFs) that act in the cytoplasm. The mechanisms of DNAAF action remain poorly defined. Here, we show that DNAAFs concentrate together with axonemal dyneins and chaperones into organelles that form specifically in multiciliated cells, which we term DynAPs, for dynein axonemal particles. These organelles display hallmarks of biomolecular condensates, and remarkably, DynAPs are enriched for the stress granule protein G3bp1, but not for other stress granule proteins or P-body proteins. Finally, we show that both the formation and the liquid-like behaviors of DynAPs are disrupted in a model of motile ciliopathy. These findings provide a unifying cell biological framework for a poorly understood class of human disease genes and add motile ciliopathy to the growing roster of human diseases associated with disrupted biological phase separation.
journal_name
Elifejournal_title
eLifeauthors
Huizar RL,Lee C,Boulgakov AA,Horani A,Tu F,Marcotte EM,Brody SL,Wallingford JBdoi
10.7554/eLife.38497subject
Has Abstractpub_date
2018-12-18 00:00:00issn
2050-084Xpii
38497journal_volume
7pub_type
杂志文章相关文献
eLife文献大全abstract::LAMP1 and LAMP2 proteins are highly abundant, ubiquitous, mammalian proteins that line the lysosome limiting membrane, and protect it from lysosomal hydrolase action. LAMP2 deficiency causes Danon's disease, an X-linked hypertrophic cardiomyopathy. LAMP2 is needed for chaperone-mediated autophagy, and its expression i...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.21635
更新日期:2016-09-24 00:00:00
abstract::How proteins harness mechanical force to control function is a significant biological question. Here we describe a human cell surface receptor that couples ligand binding and force to trigger a chemical event which controls the adhesive properties of the receptor. Our studies of the secreted platelet oxidoreductase, E...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.34843
更新日期:2018-06-22 00:00:00
abstract::The actomyosin ring generates force to ingress the cytokinetic cleavage furrow in animal cells, yet its filament organization and the mechanism of contractility is not well understood. We quantified actin filament order in human cells using fluorescence polarization microscopy and found that cleavage furrow ingression...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.30867
更新日期:2017-11-06 00:00:00
abstract::Cranial neural crest (CNC) cells give rise to bone, cartilage, tendons, and ligaments of the vertebrate craniofacial musculoskeletal complex, as well as regulate mesoderm-derived craniofacial muscle development through cell-cell interactions. Using the mouse soft palate as a model, we performed an unbiased single-cell...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.62387
更新日期:2021-01-22 00:00:00
abstract::Recent work draws attention to community-community encounters ('coalescence') as likely an important factor shaping natural ecosystems. This work builds on MacArthur's classic model of competitive coexistence to investigate such community-level competition in a minimal theoretical setting. It is shown that the ability...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.15747
更新日期:2016-06-16 00:00:00
abstract::hIAPP fibrils are associated with Type-II Diabetes, but the link of hIAPP structure to islet cell death remains elusive. Here we observe that hIAPP fibrils are cytotoxic to cultured pancreatic β-cells, leading us to determine the structure and cytotoxicity of protein segments composing the amyloid spine of hIAPP. Usin...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.19273
更新日期:2017-01-03 00:00:00
abstract::Understanding how virus capsids assemble around their nucleic acid (NA) genomes could promote efforts to block viral propagation or to reengineer capsids for gene therapy applications. We develop a coarse-grained model of capsid proteins and NAs with which we investigate assembly dynamics and thermodynamics. In contra...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.00632
更新日期:2013-06-14 00:00:00
abstract::During inflammation, serum amyloid A proteins transport retinol to infected tissues. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.04246
更新日期:2014-09-02 00:00:00
abstract::Linking interindividual differences in psychological phenotype to variations in brain structure is an old dream for psychology and a crucial question for cognitive neurosciences. Yet, replicability of the previously-reported 'structural brain behavior' (SBB)-associations has been questioned, recently. Here, we conduct...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.43464
更新日期:2019-03-13 00:00:00
abstract::Although mRNAs are localized in the processes of excitatory neurons, it is still unclear whether interneurons also localize a large population of mRNAs. In addition, the variability in the localized mRNA population within and between cell types is unknown. Here we describe the unbiased transcriptomic characterization ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.63092
更新日期:2021-01-06 00:00:00
abstract::One of the major unanswered questions in evolutionary biology is when and how the transition between diderm (two membranes) and monoderm (one membrane) cell envelopes occurred in Bacteria. The Negativicutes and the Halanaerobiales belong to the classically monoderm Firmicutes, but possess outer membranes with lipopoly...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.14589
更新日期:2016-08-31 00:00:00
abstract::Telomerase extends telomere sequences at chromosomal ends to protect genomic DNA. During this process it must select the correct nucleotide from a pool of nucleotides with various sugars and base pairing properties, which is critically important for the proper capping of telomeric sequences by shelterin. Unfortunately...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.55438
更新日期:2020-06-05 00:00:00
abstract::During embryogenesis, chromatin accessibility profiles control lineage-specific gene expression by modulating transcription, thus impacting multipotent progenitor states and subsequent fate choices. Subsets of cardiac and pharyngeal/head muscles share a common origin in the cardiopharyngeal mesoderm, but the chromatin...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.49921
更新日期:2019-11-20 00:00:00
abstract::The gonadotropin-releasing hormone (GnRH) neurons exhibit pulse and surge modes of activity to control fertility. They also exhibit an unusual bipolar morphology comprised of a classical soma-proximal dendritic zone and an elongated secretory process that can operate as both a dendrite and an axon, termed a 'dendron'....
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.53945
更新日期:2020-07-09 00:00:00
abstract::Individual recognition (IR) is essential for maintaining various social interactions in a group, and face recognition is one of the most specialised cognitive abilities in IR. We used both a mating preference system and an electric shock conditioning experiment to test IR ability in medaka, and found that signals near...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.24728
更新日期:2017-07-11 00:00:00
abstract::To move the body, the brain must precisely coordinate patterns of activity among diverse populations of motor neurons. Here, we use in vivo calcium imaging, electrophysiology, and behavior to understand how genetically-identified motor neurons control flexion of the fruit fly tibia. We find that leg motor neurons exhi...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.56754
更新日期:2020-06-03 00:00:00
abstract::β-Propellers arise through the amplification of a supersecondary structure element called a blade. This process produces toroids of between four and twelve repeats, which are almost always arranged sequentially in a single polypeptide chain. We found that new propellers evolve continuously by amplification from single...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.49853
更新日期:2019-10-15 00:00:00
abstract::The phylogenetic placement of the morphologically simple placozoans is crucial to understanding the evolution of complex animal traits. Here, we examine the influence of adding new genomes from placozoans to a large dataset designed to study the deepest splits in the animal phylogeny. Using site-heterogeneous substitu...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.36278
更新日期:2018-10-30 00:00:00
abstract::Comparing the brains of related species faces the challenges of establishing homologies whilst accommodating evolutionary specializations. Here we propose a general framework for understanding similarities and differences between the brains of primates. The approach uses white matter blueprints of the whole cortex bas...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.35237
更新日期:2018-05-11 00:00:00
abstract::Microtubules control different aspects of cell polarization. In cells with a radial microtubule system, a pivotal role in setting up asymmetry is attributed to the relative positioning of the centrosome and the nucleus. Here, we show that centrosome loss had no effect on the ability of endothelial cells to polarize an...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.33864
更新日期:2018-03-16 00:00:00
abstract::Temporary circuits amplify spontaneous activity in the visual system of neonatal rats. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.21236
更新日期:2016-10-11 00:00:00
abstract::Jellyfish, with their tetraradial symmetry, offer a novel paradigm for addressing patterning mechanisms during regeneration. Here we show that an interplay between mechanical forces, cell migration and proliferation allows jellyfish fragments to regain shape and functionality rapidly, notably by efficient restoration ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.54868
更新日期:2020-09-07 00:00:00
abstract::Microtubule dynamics facilitate neurite growth and establish morphology, but the role of minus-end binding proteins in these processes is largely unexplored. CAMSAP homologs associate with microtubule minus-ends, and are important for the stability of epithelial cell adhesions. In this study, we report morphological d...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.01637
更新日期:2014-02-25 00:00:00
abstract::Although respiratory syncytial virus (RSV) is responsible for more human deaths each year than influenza, its pathogenic mechanisms are poorly understood. Here high-resolution quantitative imaging, bioenergetics measurements and mitochondrial membrane potential- and redox-sensitive dyes are used to define RSV's impact...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.42448
更新日期:2019-06-27 00:00:00
abstract::SynGAP is a postsynaptic density (PSD) protein that binds to PDZ domains of the scaffold protein PSD-95. We previously reported that heterozygous deletion of Syngap1 in mice is correlated with increased steady-state levels of other key PSD proteins that bind PSD-95, although the level of PSD-95 remains constant (Walku...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.52656
更新日期:2020-01-15 00:00:00
abstract::Yeast cells undergoing the diauxic response show a striking upstream shift in poly(A) site utilization, with increased use of ORF-proximal poly(A) sites resulting in shorter 3' mRNA isoforms for most genes. This altered poly(A) pattern is extremely similar to that observed in cells containing Pol II derivatives with s...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.59810
更新日期:2020-08-26 00:00:00
abstract::Binary fission has been well studied in rod-shaped bacteria, but the mechanisms underlying cell division in spherical bacteria are poorly understood. Rod-shaped bacteria harbor regulatory proteins that place and remodel the division machinery during cytokinesis. In the spherical human pathogen Staphylococcus aureus, w...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.38856
更新日期:2018-10-02 00:00:00
abstract::Fruit fly neuroblasts can either self-renew, rest or take on a specialized form, depending on the levels of a protein called Prospero. ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.04869
更新日期:2014-10-29 00:00:00
abstract::During translation elongation, the ribosome ratchets along its mRNA template, incorporating each new amino acid and translocating from one codon to the next. The elongation cycle requires dramatic structural rearrangements of the ribosome. We show here that deep sequencing of ribosome-protected mRNA fragments reveals ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.01257
更新日期:2014-05-09 00:00:00
abstract::To restore vision for the blind, several prosthetic approaches have been explored that convey raw images to the brain. So far, these schemes all suffer from a lack of bandwidth. An alternate approach would restore vision at the cognitive level, bypassing the need to convey sensory data. A wearable computer captures vi...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.37841
更新日期:2018-11-27 00:00:00