Abstract:
:Synchronized beating of cilia on multiciliated cells (MCCs) generates a directional flow of mucus across epithelia. This motility requires a "9 + 2" microtubule (MT) configuration in axonemes and the unidirectional array of basal bodies of cilia on the MCCs. However, it is not fully understood what components are needed for central MT-pair assembly as they are not continuous with basal bodies in contrast to the nine outer MT doublets. In this study, we discovered that a homozygous knockdown mouse model for MT minus-end regulator calmodulin-regulated spectrin-associated protein 3 (CAMSAP3), Camsap3 tm1a/tm1a , exhibited multiple phenotypes, some of which are typical of primary ciliary dyskinesia (PCD), a condition caused by motile cilia defects. Anatomical examination of Camsap3 tm1a/tm1a mice revealed severe nasal airway blockage and abnormal ciliary morphologies in nasal MCCs. MCCs from different tissues exhibited defective synchronized beating and ineffective generation of directional flow likely underlying the PCD-like phenotypes. In normal mice, CAMSAP3 localized to the base of axonemes and at the basal bodies in MCCs. However, in Camsap3 tm1a/tm1a , MCCs lacked CAMSAP3 at the ciliary base. Importantly, the central MT pairs were missing in the majority of cilia, and the polarity of the basal bodies was disorganized. These phenotypes were further confirmed in MCCs of Xenopus embryos when CAMSAP3 expression was knocked down by morpholino injection. Taken together, we identified CAMSAP3 as being important for the formation of central MT pairs, proper orientation of basal bodies, and synchronized beating of motile cilia.
journal_name
Proc Natl Acad Sci U S Aauthors
Robinson AM,Takahashi S,Brotslaw EJ,Ahmad A,Ferrer E,Procissi D,Richter CP,Cheatham MA,Mitchell BJ,Zheng Jdoi
10.1073/pnas.1907335117subject
Has Abstractpub_date
2020-06-16 00:00:00pages
13571-13579issue
24eissn
0027-8424issn
1091-6490pii
1907335117journal_volume
117pub_type
杂志文章abstract::The rapidly expanding network of roads into the Amazon is permanently altering the world's largest tropical forest. Most proposed road projects lack rigorous impact assessments or even basic economic justification. This study analyzes the expected environmental, social and economic impacts of 75 road projects, totalin...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1910853117
更新日期:2020-03-31 00:00:00
abstract::Two clusters of configurations of the main proteolytic subunit β5 were identified by principal component analysis of crystal structures of the yeast proteasome core particle (yCP). The apo-cluster encompasses unliganded species and complexes with nonpeptidic ligands, and the pep-cluster comprises complexes with peptid...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1408018111
更新日期:2014-07-01 00:00:00
abstract::In 2005 four outstanding multiple burials were discovered near Eulau, Germany. The 4,600-year-old graves contained groups of adults and children buried facing each other. Skeletal and artifactual evidence and the simultaneous interment of the individuals suggest the supposed families fell victim to a violent event. In...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 历史文章,杂志文章
doi:10.1073/pnas.0807592105
更新日期:2008-11-25 00:00:00
abstract::Electron transfer dissociation (ETD) is a recently introduced mass spectrometric technique that provides a more comprehensive coverage of peptide sequences and posttranslational modifications. Here, we evaluated the use of ETD for a global phosphoproteome analysis. In all, we identified a total of 1,435 phosphorylatio...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0611217104
更新日期:2007-02-13 00:00:00
abstract::Cyclic AMP levels increase abruptly in the secondary palatal shelf (mesenchyme plus a two- to three-cell-layered epithelium) between day 15 and 16 of gestation in the rat embryo. The addition of dibutyryl cyclic AMP to the media in which immature palatal shelves (day 14) are cultured causes a precocious decrease in DN...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.72.3.874
更新日期:1975-03-01 00:00:00
abstract::Application of hydrostatic pressure shifts protein conformational equilibria in a direction to reduce the volume of the system. A current view is that the volume reduction is dominated by elimination of voids or cavities in the protein interior via cavity hydration, although an alternative mechanism wherein cavities a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1506505112
更新日期:2015-05-12 00:00:00
abstract::Methylation on lysine 9 of histone H3 (H3K9me) and DNA methylation play important roles in the transcriptional silencing of specific genes and repetitive elements. Both marks are detected on class I and II endogenous retroviruses (ERVs) in murine embryonic stem cells (mESCs). Recently, we reported that the H3K9-specif...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1014660108
更新日期:2011-04-05 00:00:00
abstract::The concentration of triglyceride-rich lipoproteins containing apolipoprotein (apo) B-48 (chylomicrons) and apo B-100 (very low density lipoproteins) was measured in blood plasma of healthy young men after an ordinary meal containing one-third of daily energy and fat. Plasma obtained in the postabsorptive state and at...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.5.2069
更新日期:1993-03-01 00:00:00
abstract::Histone methyltransferase G9a has critical roles in promoting cancer-cell growth and gene suppression, but whether it is also associated with the DNA damage response is rarely studied. Here, we report that loss of G9a impairs DNA damage repair and enhances the sensitivity of cancer cells to radiation and chemotherapeu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1700694114
更新日期:2017-07-25 00:00:00
abstract::The protein kinase A stimulator cAMP can potentiate the ability of progestins to induce the transactivation function of the human progesterone receptor (hPR). We questioned in the present study whether cAMP could functionally cooperate with the progestin antagonist RU486. In T47D human breast cancer cells, RU486 behav...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.10.4441
更新日期:1993-05-15 00:00:00
abstract::To determine which of seven library design algorithms best introduces new protein function without destroying it altogether, seven combinatorial libraries of green fluorescent protein variants were designed and synthesized. Each was evaluated by distributions of emission intensity and color compiled from measurements ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0609647103
更新日期:2007-01-02 00:00:00
abstract::Ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (iGluRs) mediate the majority of excitatory synaptic transmission in the CNS and are essential for the induction and maintenance of long-term potentiation and long-term depression, two cellular models of learning and memory. We identi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0708699104
更新日期:2007-11-13 00:00:00
abstract::Polycomb-group (Pc-G) proteins ensure late maintenance of transcriptional repression outside the expression domain of target genes in flies and vertebrates. They act in complexes, presumably by modulating chromatin structure. In Drosophila, they have been found to be associated with transcriptionally inactive loci but...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2237046100
更新日期:2003-11-11 00:00:00
abstract::The parietal cell (PC) plays an important role in normal gastric physiology and in common diseases of the stomach. Although the genes involved in acid secretion are well known, there is limited molecular information about other aspects of PC function. We have generated a comprehensive database of genes expressed prefe...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.231332398
更新日期:2001-11-20 00:00:00
abstract::The effects of NusA on the RNA polymerase contacts made by nucleotides at internal positions in the nascent RNA in Escherichia coli transcription complexes were analyzed by using the photocrosslinking nucleotide analog 5-[(4-azidophenacyl) thio]-UMP. It was placed at nucleotides between +6 and +15 in RNA transcribed f...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.11.5012
更新日期:1995-05-23 00:00:00
abstract::Clones of Friend erythroleukemia cells, characterized by the presence of 40-70% benzidine-positive cells synthesizing hemoglobin in the absence of inducing drugs, were treated with several phorbol diesters with a known range of tumor-promoting activity on mouse skin. Good correlation was found between the reported tum...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.74.7.2894
更新日期:1977-07-01 00:00:00
abstract::Retrograde axonal transport plays an important role in the maintenance of neuronal functions, but the mechanism is poorly defined partly because the constituents of the retrograde transport system and their interactions have yet to be elucidated. Of special interest is how dynein/dynactin motor proteins interact with ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0602222104
更新日期:2007-02-13 00:00:00
abstract::The infectivity of cloned hepatitis B viral DNA (HBV) has been tested in chimpanzees to identify a fully functional HBV genome and to assess the risk associated with its handling. Only one of two HBV DNA sequence variants tested was shown to be infectious. "Clone purified" virus of predicted nucleotide sequence was pr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.3.891
更新日期:1985-02-01 00:00:00
abstract::Epstein-Barr virus-induced gene 3 (EBI3) is a widely expressed IL-12p40-related protein that associates as a heterodimer with either IL-12p35 or an IL-12p35 homologue, p28, to create a new cytokine (IL-27). To define the function of EBI3 in vivo, we generated knockout mice in which the ebi3 gene was targeted by homolo...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.252648899
更新日期:2002-12-24 00:00:00
abstract::The chemical dynamics of lakes and streams affect their suitability as aquatic habitats and as water supplies for human needs. Because water quality is typically monitored only weekly or monthly, however, the higher-frequency dynamics of stream chemistry have remained largely invisible. To illuminate a wider spectrum ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1304328110
更新日期:2013-07-23 00:00:00
abstract::When light-grown seedlings of amaranth are transferred to total darkness, synthesis of the large subunit (LS) and small subunit (SS) of ribulose-1,5-bisphosphate carboxylase [RbuP(2)Case; 3-phospho-D-glycerate carboxylase (dimerizing), EC 4.1.1.39] is rapidly depressed. This reduction in RbuP(2)Case synthesis occurs i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.12.4190
更新日期:1988-06-01 00:00:00
abstract::Uncouplers are molecules with protonophoric and ionophoric capabilities that mediate coupled cyclical transport of cations--a transport that takes precedence over all other coupled processes. Uncouplers form cation-containing complexes with electrogenic ionophores that potentiate cyclical transport of cations. The mol...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.74.6.2241
更新日期:1977-06-01 00:00:00
abstract::The importance of identifying VEGF-independent pathways in pathological angiogenesis is increasingly recognized as a result of the emerging drug resistance to anti-VEGF therapies. PDGF-CC is the third member of the PDGF family discovered after more than two decades of studies on PDGF-AA and PDGF-BB. The biological fun...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1004143107
更新日期:2010-07-06 00:00:00
abstract::Mixing genomes of different species by hybridization can disrupt species-specific genetic interactions that were adapted and fixed within each species population. Such disruption can predispose the hybrids to abnormalities and disease that decrease the overall fitness of the hybrids and is therefore named as hybrid in...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2010133117
更新日期:2020-11-24 00:00:00
abstract::Life in environments devoid of photosynthesis, such as on early Earth or in contemporary dark subsurface ecosystems, is supported by chemical energy. How, when, and where chemical nutrients released from the geosphere fuel chemosynthetic biospheres is fundamental to understanding the distribution and diversity of life...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2007051117
更新日期:2021-01-12 00:00:00
abstract::We are interested in the balance of energy and protein synthesis in bacterial growth. How has evolution optimized this balance? We describe an analytical model that leverages extensive literature data on growth laws to infer the underlying fitness landscape and to draw inferences about what evolution has optimized in ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1421138111
更新日期:2015-01-13 00:00:00
abstract::The gluconate (gnt) operon of Bacillus subtilis consists of four gnt genes; the second and third genes code for gluconate kinase (gluconokinase, EC 2.7.1.12) and gluconate permease, respectively. A fragment carrying the promoter of this operon (gnt promoter) and the first gene (gntR) was subcloned into a promoter prob...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.13.4524
更新日期:1987-07-01 00:00:00
abstract::This study presents, to our knowledge, the first on-line measurement of acetylcholinesterase (AcChoEase) release from brain tissue. It is now well established that a soluble form of the enzyme is released from central nervous system neurons, and it has been proposed on indirect grounds that such release may occur not ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.9.3047
更新日期:1987-05-01 00:00:00
abstract::Spectrin is an important structural component of the plasma membrane skeleton. Heretofore-unidentified isoforms of spectrin also associate with Golgi and other organelles. We have discovered another member of the beta-spectrin gene family by homology searches of the GenBank databases and by 5' rapid amplification of c...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.24.14158
更新日期:1998-11-24 00:00:00
abstract::A computer code to investigate the equilibrium and stability of a diffuse plasma in three dimensions is described that generalizes earlier work on a sharp free boundary model. Toroidal equilibria of a plasma are determined by considering paths of steepest descent associated with a new version of the variational princi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.73.4.984
更新日期:1976-04-01 00:00:00