Abstract:
:Individual cell types are defined by architecturally and functionally specialized cortical domains. The Ezrin, Radixin, and Moesin (ERM) proteins play a major role in organizing cortical domains by assembling membrane protein complexes and linking them to the cortical actin cytoskeleton. Many studies have focused on the individual roles of the ERM proteins in stabilizing the membrane-cytoskeleton interface, controlling the distribution and function of apical membrane complexes, regulating the small GTPase Rho, or establishing cell-cell junctions. We previously found that deletion of the mouse Ezrin gene yields severe defects in apical integrity throughout the developing intestinal epithelium, resulting in incomplete villus morphogenesis and neonatal death. However, the molecular function of Ezrin in building the apical surface of the intestinal epithelium was not clear. By deleting Ezrin in the adult mouse intestinal epithelium, we provide evidence that Ezrin performs multiple molecular functions that collaborate to build the functional apical surface of the intestinal epithelium in vivo. The loss of Ezrin-mediated apical integrity in the adult intestine yields severe morphological consequences during intestinal homeostasis, including defects in cell geometry, extrusion, junctional remodeling, and spindle orientation. Surprisingly, deletion of Ezrin either before or after villus morphogenesis yields villus fusion, revealing a previously unrecognized step in intestinal homeostasis. Our studies indicate that the function of Ezrin in building and maintaining the apical domain is essential not only for intestinal morphogenesis but also for homeostasis in the mature intestine.
journal_name
Proc Natl Acad Sci U S Aauthors
Casaletto JB,Saotome I,Curto M,McClatchey AIdoi
10.1073/pnas.1103418108subject
Has Abstractpub_date
2011-07-19 00:00:00pages
11924-9issue
29eissn
0027-8424issn
1091-6490pii
1103418108journal_volume
108pub_type
杂志文章abstract::The expression of interleukin 2 receptors (IL-2R) is a critical step leading to normal lymphocyte proliferation. Since thymosin fraction 5 (TF5), a thymic hormone preparation, enhances lymphoproliferative responses of human cells, we examined the effects of TF5 on the expression of IL-2R on mitogen-stimulated human ly...
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.83.16.6107
更新日期:1986-08-01 00:00:00
abstract::The hypothalamic arcuate nucleus is involved in the control of energy intake and expenditure and may participate in the pathogenesis of eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). Two systems are of particular interest in this respect, synthesizing alpha-melanocyte-stimulating hormone (alp...
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.222658699
更新日期:2002-12-24 00:00:00
abstract::Diverse forms of injury and stress evoke a hypertrophic growth response in adult cardiac myocytes, which is characterized by an increase in cell size, enhanced protein synthesis, assembly of sarcomeres, and reactivation of fetal genes, often culminating in heart failure and sudden death. Given the emerging roles of mi...
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.0608791103
更新日期:2006-11-28 00:00:00
abstract::A photolyzable derivative of dipeptidyl-tRNA, p-azido-N-tBoc-Phe-[3H]Phe-tRNA, bound reversibly to 70S ribosomes in the presence of poly(U), becomes, when irradiated, covalently attached to components of the 50S ribosomal subunit. Most of the reaction occurs within the 23S RNA, while ribosomal proteins are only weakly...
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.72.11.4332
更新日期:1975-11-01 00:00:00
abstract::An intermolecular intercalation of base pairs was found at the CA step in the I222 crystal structure of the RNA.DNA hybrid, r(CAAAGAAAAG).d(CTTTTCTTTG), which contains two-thirds of the polypurine tract sequence of HIV-1 with a substitution of cytosine for the initial adenine. This sequence crystallized in both P21212...
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.1533326100
更新日期:2003-08-05 00:00:00
abstract::Valproic acid (VPA) is an anticonvulsant drug that is also used to treat migraines and bipolar disorder. Its proposed biological targets include human voltage-gated sodium channels, among other membrane proteins. We used the prokaryotic NavMs sodium channel, which has been shown to be a good exemplar for drug binding ...
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.1909696116
更新日期:2019-12-10 00:00:00
abstract::The mucopolysaccharidoses are a group of genetic diseases characterized by storage of incompletely degraded glycosaminoglycans. Such storage causes marked distortion of many tissues with consequent severe somatic changes and mental retardation. Storage of glycosaminoglycans results from markedly diminished activity of...
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.73.2.630
更新日期:1976-02-01 00:00:00
abstract::Homopyrimidine oligonucleotides bind to the major groove of a complementary homopyrimidine.homopurine stretch by triple helix formation. The bla gene from transposon Tn3 contains a homopyrimidine.homopurine sequence of 13 base pairs located just downstream of the RNA polymerase binding site. A 13-mer homopyrimidine ol...
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.89.2.504
更新日期:1992-01-15 00:00:00
abstract::Dematerialization, represented by declining consumption per GDP of energy or of goods, offers some hope for rising environmental quality with development. The declining proportion of income spent on staples as affluence grows, which income elasticity <1.0 measures, makes dematerialization widespread. Further, as learn...
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.0806099105
更新日期:2008-09-02 00:00:00
abstract::Both laboratory and field data suggest that people punish noncooperators even in one-shot interactions. Although such "altruistic punishment" may explain the high levels of cooperation in human societies, it creates an evolutionary puzzle: existing models suggest that altruistic cooperation among nonrelatives is evolu...
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.0630443100
更新日期:2003-03-18 00:00:00
abstract::To use recombinant DNA technology to functionally analyze mutations introduced into cloned eukaryotic genes, a rapid procedure is necessary to assay the steps along the gene expression pathway. Since cloned rat insulin genes are not transcribed efficiently after transfection into various cell lines, I have asked wheth...
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.79.19.5798
更新日期:1982-10-01 00:00:00
abstract::Tolerance and resistance provide hosts with two distinct defense strategies against parasitism. In resistance the hosts "fight" the parasite directly, whereas in tolerance the hosts fight the disease by ameliorating the damage that infection causes. There is increasing recognition that the two mechanisms may exhibit v...
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.0809558105
更新日期:2008-12-30 00:00:00
abstract::Human low density lipoproteins (LDL) are the major cholesterol carriers in the blood. Elevated concentration of LDL is a major risk factor for atherosclerotic disease. Purified LDL particles appear heterogeneous in images obtained with a 400-kV electron cryomicroscope. Using multivariate statistical and cluster analys...
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.96.15.8420
更新日期:1999-07-20 00:00:00
abstract::Measles virus (MeV) is the poster child for acute infection followed by lifelong immunity. However, recent work shows the presence of MeV RNA in multiple sites for up to 3 mo after infection in a proportion of infected children. Here, we use experimental infection of rhesus macaques to show that prolonged RNA presence...
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.1211138109
更新日期:2012-09-11 00:00:00
abstract::Within the mammalian testis, specialized tight junctions between somatic Sertoli cells create basal and apical polarity within the cells, restrict movement of molecules between cells, and separate the seminiferous epithelium into basal and adluminal compartments. These tight junctions form the basis of the blood-testi...
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.0506084102
更新日期:2005-11-15 00:00:00
abstract::Mutations are a hallmark of cancer. Normal cells minimize spontaneous mutations through the combined actions of polymerase base selectivity, 3' --> 5' exonucleolytic proofreading, mismatch correction, and DNA damage repair. To determine the consequences of defective proofreading in mammals, we created mice with a poin...
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.232340999
更新日期:2002-11-26 00:00:00
abstract::Targeted gene modification mediated by single-stranded oligonucleotides (SSOs) holds great potential for widespread use in a number of biological and biomedical fields, including functional genomics and gene therapy. By using this approach, specific genetic changes have been created in a number of prokaryotic and euka...
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.0406991102
更新日期:2005-02-15 00:00:00
abstract::Using a diverse collection of small molecules we recently found that compound sets from different sources (commercial; academic; natural) have different protein-binding behaviors, and these behaviors correlate with trends in stereochemical complexity for these compound sets. These results lend insight into structural ...
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.1015024108
更新日期:2011-04-26 00:00:00
abstract::Ubiquitin E3 ligases are crucial for eliminating misfolded proteins before they form cytotoxic aggregates that threaten cell fitness and survival. However, it remains unclear how emerging misfolded proteins in the cytoplasm can be selectively recognized and eliminated by E3 ligases in plants. We found that Misfolded P...
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.1713574114
更新日期:2017-11-14 00:00:00
abstract::Molecular beacons are FRET-based target-activatable probes. They offer control of fluorescence emission in response to specific cancer targets, thus are useful tools for in vivo cancer imaging. Photodynamic therapy (PDT) is a cell-killing process by light activation of a photosensitizer (PS) in the presence of oxygen....
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.0611142104
更新日期:2007-05-22 00:00:00
abstract::Administration of gamma-glutamylcysteinylglycyl monomethyl (or monoethyl) ester to mice leads to substantial increases in the levels of glutathione in the liver and kidney. Mice depleted of glutathione by treatment with buthionine sulfoximine, a potent inhibitor of gamma-glutamylcysteine synthetase, exhibited about 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.80.17.5258
更新日期:1983-09-01 00:00:00
abstract::The Japanese firefly squid, Watasenia scintillans, emits intense flashes of light from three tiny luminous organs that are located at the tip of each of a pair of ventral arms. Light is also produced from hundreds of other minute organs that are scattered over the body. The luminescence is due to an ATP-dependent reac...
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.82.14.4629
更新日期:1985-07-01 00:00:00
abstract::The effect of tumor promoters on electrical coupling between human FL cells was investigated with a microelectrode technique. When a low concentration (100 ng/ml) of 12-O-tetradecanoylphorbol 13-acetate (TPA) was added to culture medium, only 6% of the cells showed electrical coupling after 5 hr, whereas in control me...
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.78.9.5628
更新日期:1981-09-01 00:00:00
abstract::Although(,) vascular remodeling is a hallmark of many chronic inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis, anti-vascular strategies to treat these conditions have received little attention to date. We investigated the anti-inflammatory activity of systemic blockade 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.0907550106
更新日期:2009-12-15 00:00:00
abstract::The previously described peptide material that reacts with antibodies to gastrin and is found in the central nervous system of various vertebrates is present in only the 100,000 X g pellet of postmortem human cerebral cortical grey matter. This immunoreactive material, extractable in boiling water, is biologically act...
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.75.1.524
更新日期:1978-01-01 00:00:00
abstract::A fragment of the cloned gene for the human myeloma ND epsilon chain, coding for the second, third, and fourth domains of the immunoglobulin, has been coupled to the tryptophan control region of an expression plasmid and subcloned in Escherichia coli. Induction of gene expression results in the synthesis of the expect...
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.81.10.2955
更新日期:1984-05-01 00:00:00
abstract::Protein kinase A (PKA) is activated during sympathetic stimulation of the heart and phosphorylates key proteins involved in cardiac Ca(2+) handling, including the L-type Ca(2+) channel (Ca(V)1.2) and phospholamban (PLN). This results in acceleration and amplification of the beat-to-beat changes in cytosolic Ca(2+) 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.1215219109
更新日期:2012-10-16 00:00:00
abstract::The cytoplasmic Myc protein (c-Myc) regulates various human genes and is dysregulated in many human cancers. Phosphorylation mediates the protein activation of c-Myc and is essential for the function of this transcription factor in normal cell behavior and tumor growth. To date, however, the targeting of Myc as a ther...
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.1007443107
更新日期:2010-09-07 00:00:00
abstract::The maytansinoid drug DM1 is 100- to 1000-fold more cytotoxic than anticancer drugs that are currently in clinical use. The immunoconjugate C242-DM1 was prepared by conjugating DM1 to the monoclonal antibody C242, which recognizes a mucin-type glycoprotein expressed to various extents by human colorectal cancers. C242...
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.93.16.8618
更新日期:1996-08-06 00:00:00
abstract::Actin polymerization and assembly into stress fibers (SFs) is central to many cellular processes. However, how SFs form in response to the mechanical interaction of cells with their environment is not fully understood. Here we have identified Piezo2 mechanosensitive cationic channel as a transducer of environmental ph...
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.1718177115
更新日期:2018-02-20 00:00:00