Drosophila as a model for studying cystic fibrosis pathophysiology of the gastrointestinal system.

Abstract:

:Cystic fibrosis (CF) is a recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. The most common symptoms include progressive lung disease and chronic digestive conditions. CF is the first human genetic disease to benefit from having five different species of animal models. Despite the phenotypic differences among the animal models and human CF, these models have provided invaluable insight into understanding disease mechanisms at the organ-system level. Here, we identify a member of the ABCC4 family, CG5789, that has the structural and functional properties expected for encoding the Drosophila equivalent of human CFTR, and thus refer to it as Drosophila CFTR (Dmel\CFTR). We show that knockdown of Dmel\CFTR in the adult intestine disrupts osmotic homeostasis and displays CF-like phenotypes that lead to intestinal stem cell hyperplasia. We also show that expression of wild-type human CFTR, but not mutant variants of CFTR that prevent plasma membrane expression, rescues the mutant phenotypes of Dmel\CFTR Furthermore, we performed RNA sequencing (RNA-Seq)-based transcriptomic analysis using Dmel\CFTR fly intestine and identified a mucin gene, Muc68D, which is required for proper intestinal barrier protection. Altogether, our findings suggest that Drosophila can be a powerful model organism for studying CF pathophysiology.

authors

Kim K,Lane EA,Saftien A,Wang H,Xu Y,Wirtz-Peitz F,Perrimon N

doi

10.1073/pnas.1913127117

subject

Has Abstract

pub_date

2020-05-12 00:00:00

pages

10357-10367

issue

19

eissn

0027-8424

issn

1091-6490

pii

1913127117

journal_volume

117

pub_type

杂志文章
  • Comparison of predicted and actual consequences of missense mutations.

    abstract::Each person's genome sequence has thousands of missense variants. Practical interpretation of their functional significance must rely on computational inferences in the absence of exhaustive experimental measurements. Here we analyzed the efficacy of these inferences in 33 de novo missense mutations revealed by sequen...

    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.1511585112

    authors: Miosge LA,Field MA,Sontani Y,Cho V,Johnson S,Palkova A,Balakishnan B,Liang R,Zhang Y,Lyon S,Beutler B,Whittle B,Bertram EM,Enders A,Goodnow CC,Andrews TD

    更新日期:2015-09-15 00:00:00

  • Promoter-regulatory region of the major immediate early gene of human cytomegalovirus.

    abstract::The DNA templates containing immediate early (IE) genes of human cytomegalovirus (CMV) were transcribed in vitro by using a HeLa cell extract. When IE region 1, 2, and 3 were used, transcription was detected qualitatively only from IE region 1. Transcription was detected with DNA representing IE region 2 when the IE r...

    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.81.3.659

    authors: Thomsen DR,Stenberg RM,Goins WF,Stinski MF

    更新日期:1984-02-01 00:00:00

  • Mobility and distribution of a cell surface glycoprotein and its interaction with other membrane components.

    abstract::Fluorescence photobleaching recovery and immunofluorescence methods have been used to study the lateral mobility and topographical distribution of a major cell surface glycoprotein (CSP). Both endogenous CSP and fluorescent-labeled exogenous CSP bind to the cell surface in a fibrillar pattern and are immobile on the e...

    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.74.7.2909

    authors: Schlessinger J,Barak LS,Hammes GG,Yamada KM,Pastan I,Webb WW,Elson EL

    更新日期:1977-07-01 00:00:00

  • Rotavirus mRNAS are released by transcript-specific channels in the double-layered viral capsid.

    abstract::Rotaviruses are the single most common cause of fatal and severe childhood diarrheal illness worldwide (>125 million cases annually). Rotavirus shares structural and functional features with many viruses, such as the presence of segmented double-stranded RNA genomes selectively and tightly packed with a conserved numb...

    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.1220345110

    authors: Periz J,Celma C,Jing B,Pinkney JN,Roy P,Kapanidis AN

    更新日期:2013-07-16 00:00:00

  • Facebook language predicts depression in medical records.

    abstract::Depression, the most prevalent mental illness, is underdiagnosed and undertreated, highlighting the need to extend the scope of current screening methods. Here, we use language from Facebook posts of consenting individuals to predict depression recorded in electronic medical records. We accessed the history of Faceboo...

    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.1802331115

    authors: Eichstaedt JC,Smith RJ,Merchant RM,Ungar LH,Crutchley P,Preoţiuc-Pietro D,Asch DA,Schwartz HA

    更新日期:2018-10-30 00:00:00

  • Temperature increase of 21st century mitigation scenarios.

    abstract::Estimates of 21st Century global-mean surface temperature increase have generally been based on scenarios that do not include climate policies. Newly developed multigas mitigation scenarios, based on a wide range of modeling approaches and socioeconomic assumptions, now allow the assessment of possible impacts of clim...

    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.0711129105

    authors: Van Vuuren DP,Meinshausen M,Plattner GK,Joos F,Strassmann KM,Smith SJ,Wigley TM,Raper SC,Riahi K,de la Chesnaye F,den Elzen MG,Fujino J,Jiang K,Nakicenovic N,Paltsev S,Reilly JM

    更新日期:2008-10-07 00:00:00

  • Global warming accelerates uptake of atmospheric mercury in regions experiencing glacier retreat.

    abstract::As global climate continues to warm, melting of glaciers releases a large quantity of mercury (Hg) originally locked in ice into the atmosphere and downstream ecosystems. Here, we show an opposite process that captures atmospheric Hg through glacier-to-vegetation succession. Our study using stable isotope techniques 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.1906930117

    authors: Wang X,Luo J,Yuan W,Lin CJ,Wang F,Liu C,Wang G,Feng X

    更新日期:2020-01-28 00:00:00

  • Exon/intron organization and complete nucleotide sequence of an HLA gene.

    abstract::We have isolated and determined the sequence of a genomic clone containing the gene for a human class I transplantation antigen. The gene contains seven exons. The first five exons code respectively for a signal peptide, for the first, second, and third extracellular domains of the protein molecule, and for the transm...

    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.79.3.893

    authors: Malissen M,Malissen B,Jordan BR

    更新日期:1982-02-01 00:00:00

  • Assembly of the functional membrane attack complex of human complement: formation of disulfide-linked C9 dimers.

    abstract::The 158,000 Mr protein, previously designated C5c, present in fully assembled complement (C) membrane attack complexes (MC5b-9) has been identified as a disulfide-bonded dimer of C9. This conclusion was based on the observations that: (i) a portion of the 125I-radiolabeled precursor C9 incorporated into MC5b-9 complex...

    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.78.10.6426

    authors: Ware CF,Kolb WP

    更新日期:1981-10-01 00:00:00

  • A nuclear factor containing the leucine-rich repeats expressed in murine cerebellar neurons.

    abstract::A nuclear protein, termed leucine-rich acidic nuclear protein (LANP), has been isolated from among rat cerebellar proteins whose expression was transiently increased during an early stage of postnatal development. The amino acid sequence, deduced from its cDNA, showed that LANP contains 247 amino acids consisting of t...

    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.91.21.9670

    authors: Matsuoka K,Taoka M,Satozawa N,Nakayama H,Ichimura T,Takahashi N,Yamakuni T,Song SY,Isobe T

    更新日期:1994-10-11 00:00:00

  • Logarithm of odds (lods) for linkage in complex inheritance.

    abstract::Lod scores provide a method to unify linkage tests based on identity by descent and identity in marker state while permitting selection of the most informative individuals through their disease-related phenotypes and markers in relatives. After parametric lods are reviewed, a nonparametric approach that depends on a s...

    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.93.8.3471

    authors: Morton NE

    更新日期:1996-04-16 00:00:00

  • Unifying mechanism for different fibrotic diseases.

    abstract::Fibrotic diseases are not well-understood. They represent a number of different diseases that are characterized by the development of severe organ fibrosis without any obvious cause, such as the devastating diseases idiopathic pulmonary fibrosis (IPF) and scleroderma. These diseases have a poor prognosis comparable wi...

    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.1621375114

    authors: Wernig G,Chen SY,Cui L,Van Neste C,Tsai JM,Kambham N,Vogel H,Natkunam Y,Gilliland DG,Nolan G,Weissman IL

    更新日期:2017-05-02 00:00:00

  • Promoters regulated by the glnG (ntrC) and nifA gene products share a heptameric consensus sequence in the -15 region.

    abstract::We have determined the nucleotide sequences of the Klebsiella pneumoniae nifL (regulation of N2 fixation genes) and the Escherichia coli glnA (glutamine synthetase) promoters. We compared these sequences with the published sequences of three other promoters that, like the nifL and glnA promoters, are activated by the ...

    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.80.9.2524

    authors: Ow DW,Sundaresan V,Rothstein DM,Brown SE,Ausubel FM

    更新日期:1983-05-01 00:00:00

  • Nonexponential kinetics of a single tRNAPhe molecule under physiological conditions.

    abstract::The fluorescence decay functions of individual, specifically labeled tRNAPhe molecules exhibit nonexponential character as a result of conformational dynamics occurring during the measurement on a single molecule. tRNAPhe conformational states that interchange much more slowly are evidenced by the distribution 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.94.15.7932

    authors: Jia Y,Sytnik A,Li L,Vladimirov S,Cooperman BS,Hochstrasser RM

    更新日期:1997-07-22 00:00:00

  • Yeast aconitase binds and provides metabolically coupled protection to mitochondrial DNA.

    abstract::Aconitase (Aco1p) is a multifunctional protein: It is an enzyme of the tricarboxylic acid cycle. In animal cells, Aco1p also is a cytosolic protein binding to mRNAs to regulate iron metabolism. In yeast, Aco1p was identified as a component of mtDNA nucleoids. Here we show that yeast Aco1p protects mtDNA from excessive...

    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.0703078104

    authors: Chen XJ,Wang X,Butow RA

    更新日期:2007-08-21 00:00:00

  • A note on statistical analysis of shape through triangulation of landmarks.

    abstract::In an earlier paper, the author jointly with S. Suryawanshi proposed statistical analysis of shape through triangulation of landmarks on objects. It was observed that the angles of the triangles are invariant to scaling, location, and rotation of objects. No distinction was made between an object and its reflection. T...

    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.97.7.2995

    authors: Rao CR

    更新日期:2000-03-28 00:00:00

  • A genome-scale CRISPR screen reveals factors regulating Wnt-dependent renewal of mouse gastric epithelial cells.

    abstract::An ability to safely harness the powerful regenerative potential of adult stem cells for clinical applications is critically dependent on a comprehensive understanding of the underlying mechanisms regulating their activity. Epithelial organoid cultures accurately recapitulate many features of in vivo stem cell-driven ...

    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.2016806118

    authors: Murakami K,Terakado Y,Saito K,Jomen Y,Takeda H,Oshima M,Barker N

    更新日期:2021-01-26 00:00:00

  • Gap-modulation infrared spectroscopy of high transition temperature superconductors.

    abstract::Conventional methods of determining the coupling factor alpha(2)(omega)F(omega) for the newly discovered high transition temperature (T(c)) cuprate superconductors by using tunneling and infrared measurements have thus far failed to show the cause of the very high T(c) of these compounds. This is due in part to diffic...

    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.85.13.4596

    authors: Little WA,Collman JP

    更新日期:1988-07-01 00:00:00

  • Neural dynamics of semantic composition.

    abstract::Human speech comprehension is remarkable for its immediacy and rapidity. The listener interprets an incrementally delivered auditory input, millisecond by millisecond as it is heard, in terms of complex multilevel representations of relevant linguistic and nonlinguistic knowledge. Central to this process are the neura...

    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.1903402116

    authors: Lyu B,Choi HS,Marslen-Wilson WD,Clarke A,Randall B,Tyler LK

    更新日期:2019-10-15 00:00:00

  • The SUR2 gene of Arabidopsis thaliana encodes the cytochrome P450 CYP83B1, a modulator of auxin homeostasis.

    abstract::Genetic screens have been performed to identify mutants with altered auxin homeostasis in Arabidopsis. A tagged allele of the auxin-overproducing mutant sur2 was identified within a transposon mutagenized population. The SUR2 gene was cloned and shown to encode the CYP83B1 protein, which belongs to the large family of...

    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.260502697

    authors: Barlier I,Kowalczyk M,Marchant A,Ljung K,Bhalerao R,Bennett M,Sandberg G,Bellini C

    更新日期:2000-12-19 00:00:00

  • Arachidonate lipoxygenases as essential regulators of cell survival and apoptosis.

    abstract::Arachidonic acid (AA) metabolites derived from both cyclooxygenase (COX) and lipoxygenase (LOX) pathways transduce a variety of signals related to cell growth. Here, we report that the AA LOX pathway also functions as a critical regulator of cell survival and apoptosis. Rat Walker 256 (W256) carcinosarcoma cells expre...

    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.93.11.5241

    authors: Tang DG,Chen YQ,Honn KV

    更新日期:1996-05-28 00:00:00

  • Host cell recognition by the henipaviruses: crystal structures of the Nipah G attachment glycoprotein and its complex with ephrin-B3.

    abstract::Nipah virus (NiV) and Hendra virus are the type species of the highly pathogenic paramyxovirus genus Henipavirus, which can cause severe respiratory disease and fatal encephalitis infections in humans, with case fatality rates approaching 75%. NiV contains two envelope glycoproteins, the receptor-binding G glycoprotei...

    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.0804797105

    authors: Xu K,Rajashankar KR,Chan YP,Himanen JP,Broder CC,Nikolov DB

    更新日期:2008-07-22 00:00:00

  • Gene expression during the priming phase of liver regeneration after partial hepatectomy in mice.

    abstract::Understanding the gene-expression patterns during liver regeneration may help to reveal how regenerative processes are initiated and controlled as well as shed new light onto processes that lead to liver disease. Using high-density oligonucleotide arrays, we have examined the gene-expression program in the livers of m...

    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.122359899

    authors: Su AI,Guidotti LG,Pezacki JP,Chisari FV,Schultz PG

    更新日期:2002-08-20 00:00:00

  • Reconstitution of thermostable ATPase capable of energy coupling from its purified subunits.

    abstract::Purified dicyclohexylcarbodiimide-sensitive ATPase (TF0-F1) from thermophilic bacterium PS3 is composed of a water soluble part with ATP hydrolytic activity (TF1) and a water insoluble moiety (TF0). All of the five subunits (alpha, beta, gamma, delta, and epsilon) of TF1 were isolated. TF1 was reconstituted from the 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.74.3.936

    authors: Yoshida M,Okamoto H,Sone N,Hirata H,Kagawa Y

    更新日期:1977-03-01 00:00:00

  • Defining recovery neurobiology of injured spinal cord by synthetic matrix-assisted hMSC implantation.

    abstract::Mesenchymal stromal stem cells (MSCs) isolated from adult tissues offer tangible potential for regenerative medicine, given their feasibility for autologous transplantation. MSC research shows encouraging results in experimental stroke, amyotrophic lateral sclerosis, and neurotrauma models. However, further translatio...

    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.1616340114

    authors: Ropper AE,Thakor DK,Han I,Yu D,Zeng X,Anderson JE,Aljuboori Z,Kim SW,Wang H,Sidman RL,Zafonte RD,Teng YD

    更新日期:2017-01-31 00:00:00

  • Induction of apoptotic DNA damage and cell death by activation of the sphingomyelin pathway.

    abstract::The potential involvement of ceramide-related signaling processes in the induction of apoptosis by tumor necrosis factor alpha was assessed by multiple biochemical strategies in the human leukemic cell lines HL-60 and U937 and the murine fibrosarcoma cell lines L929/LM and WEHI 164/13. Exposure of these cells to tumor...

    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.91.1.73

    authors: Jarvis WD,Kolesnick RN,Fornari FA,Traylor RS,Gewirtz DA,Grant S

    更新日期:1994-01-04 00:00:00

  • CD4 memory T cells divide poorly in response to antigen because of their cytokine profile.

    abstract::Immunological memory is a hallmark of adaptive immunity, and understanding T cell memory will be central to the development of effective cell-mediated vaccines. The characteristics and functions of CD4 memory cells have not been well defined. Here we demonstrate that the increased size of the secondary response is sol...

    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.0807449105

    authors: MacLeod MK,McKee A,Crawford F,White J,Kappler J,Marrack P

    更新日期:2008-09-23 00:00:00

  • Formation of junctions involved in excitation-contraction coupling in skeletal and cardiac muscle.

    abstract::During excitation-contraction (e-c) coupling of striated muscle, depolarization of the surface membrane is converted into Ca2+ release from internal stores. This process occurs at intracellular junctions characterized by a specialized composition and structural organization of membrane proteins. The coordinated arrang...

    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.93.15.8101

    authors: Flucher BE,Franzini-Armstrong C

    更新日期:1996-07-23 00:00:00

  • Absence of low-molecular-weight alpha crystallin in nuclear region of old human lenses.

    abstract::Examination of old human lenses indicates that low-molecular-weight alpha crystallin is not present in the inner 30-40%, the nucleus, of the lens. The remainder of such lenses, the periphery, contains normal levels of this protein. This finding is in marked contrast to observations in young lenses, where a large quant...

    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.73.10.3484

    authors: Roy D,Spector A

    更新日期:1976-10-01 00:00:00

  • DNA-membrane association is necessary for initiation of chromosomal and plasmid replication in Bacillus subtilis.

    abstract::We examined the effect of the inhibition of initiation of DNA replication on the membrane association of the chromosomal origin of replication of Bacillus subtilis and the Staphylococcus aureus-Bacillus pumilus chimeric plasmid pSL103, using temperature-sensitive mutants of B. subtilis that have specifically affected ...

    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.77.5.2834

    authors: Winston S,Sueoka N

    更新日期:1980-05-01 00:00:00