Abstract:
:Calpains constitute a superfamily of Ca2+-dependent cysteine proteases, indispensable for various cellular processes. Among the 15 mammalian calpains, calpain 8/nCL-2 and calpain 9/nCL-4 are predominantly expressed in the gastrointestinal tract and are restricted to the gastric surface mucus (pit) cells in the stomach. Possible functions reported for calpain 8 are in vesicle trafficking between ER and Golgi, and calpain 9 are implicated in suppressing tumorigenesis. These highlight that calpains 8 and 9 are regulated differently from each other and from conventional calpains and, thus, have potentially important, specific functions in the gastrointestinal tract. However, there is no direct evidence implicating calpain 8 or 9 in human disease, and their properties and physiological functions are currently unknown. To address their physiological roles, we analyzed mice with mutations in the genes for these calpains, Capn8 and Capn9. Capn8(-/-) and Capn9(-/-) mice were fertile, and their gastric mucosae appeared normal. However, both mice were susceptible to gastric mucosal injury induced by ethanol administration. Moreover, the Capn8(-/-) stomach showed significant decreases in both calpains 9 and 8, and the same was true for Capn9(-/-). Consistent with this finding, in the wild-type stomach, calpains 8 and 9 formed a complex we termed "G-calpain," in which both were essential for activity. This is the first example of a "hybrid" calpain complex. To address the physiological relevance of the calpain 8 proteolytic activity, we generated calpain 8:C105S "knock-in" (Capn8(CS/CS)) mice, which expressed a proteolytically inactive, but structurally intact, calpain 8. Although, unlike the Capn8(-/-) stomach, that of the Capn8(CS/CS) mice expressed a stable and active calpain 9, the mice were susceptible to ethanol-induced gastric injury. These results provide the first evidence that both of the gastrointestinal-tract-specific calpains are essential for gastric mucosal defense, and they point to G-calpain as a potential target for gastropathies caused by external stresses.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Hata S,Abe M,Suzuki H,Kitamura F,Toyama-Sorimachi N,Abe K,Sakimura K,Sorimachi Hdoi
10.1371/journal.pgen.1001040subject
Has Abstractpub_date
2010-07-29 00:00:00pages
e1001040issue
7eissn
1553-7390issn
1553-7404journal_volume
6pub_type
杂志文章相关文献
PLoS Genetics文献大全abstract::Meiotic recombination is essential for the repair of programmed double strand breaks (DSBs) to generate crossovers (COs) during meiosis. The efficient processing of meiotic recombination intermediates not only needs various resolvases but also requires proper meiotic chromosome structure. The Smc5/6 complex belongs to...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005872
更新日期:2016-03-24 00:00:00
abstract::The Rif1 protein is a negative regulator of DNA replication initiation in eukaryotes. Here we show that budding yeast Rif1 inhibits DNA replication initiation at the rDNA locus. Absence of Rif1, or disruption of its interaction with PP1/Glc7 phosphatase, leads to more intensive rDNA replication. The effect of Rif1-Glc...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006414
更新日期:2016-11-07 00:00:00
abstract::Histone posttranslational modifications (HPTMs) are involved in chromatin-based regulation of fungal secondary metabolite biosynthesis (SMB) in which the corresponding genes-usually physically linked in co-regulated clusters-are silenced under optimal physiological conditions (nutrient-rich) but are activated when nut...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006222
更新日期:2016-08-22 00:00:00
abstract::In flowering plants, gene expression in the haploid male gametophyte (pollen) is essential for sperm delivery and double fertilization. Pollen also undergoes dynamic epigenetic regulation of expression from transposable elements (TEs), but how this process interacts with gene expression is not clearly understood. To e...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008462
更新日期:2020-04-01 00:00:00
abstract::Curly, described almost a century ago, is one of the most frequently used markers in Drosophila genetics. Despite this the molecular identity of Curly has remained obscure. Here we show that Curly mutations arise in the gene dual oxidase (duox), which encodes a reactive oxygen species (ROS) generating NADPH oxidase. U...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005625
更新日期:2015-11-20 00:00:00
abstract::Short insertions, deletions (INDELs) and larger structural variants have been increasingly employed in genetic association studies, but few improvements over SNP-based association have been reported. In order to understand why this might be the case, we analysed two publicly available datasets and observed that 63% of...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007699
更新日期:2018-10-16 00:00:00
abstract::The dual toxicity/essentiality of copper forces cells to maintain a tightly regulated homeostasis for this metal in all living organisms, from bacteria to humans. Consequently, many genes have previously been reported to participate in copper detoxification in bacteria. Myxococcus xanthus, a prokaryote, encodes many p...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002106
更新日期:2011-06-01 00:00:00
abstract::Dietary factors, including meat, fruits, vegetables and fiber, are associated with colorectal cancer; however, there is limited information as to whether these dietary factors interact with genetic variants to modify risk of colorectal cancer. We tested interactions between these dietary factors and approximately 2.7 ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004228
更新日期:2014-04-17 00:00:00
abstract::The Cleavage Factor 1A (CF1A) complex, which is required for the termination of transcription in budding yeast, occupies the 3' end of transcriptionally active genes. We recently demonstrated that CF1A subunits also crosslink to the 5' end of genes during transcription. The presence of CF1A complex at the promoter sug...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003722
更新日期:2013-01-01 00:00:00
abstract::Mating and gametogenesis are two essential components of animal reproduction. Gametogenesis must be modulated by the need for gametes, yet little is known of how mating, a process that utilizes gametes, may modulate the process of gametogenesis. Here, we report that mating stimulates female germline stem cell (GSC) pr...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006123
更新日期:2016-06-16 00:00:00
abstract::Dermal hyperpigmentation or Fibromelanosis (FM) is one of the few examples of skin pigmentation phenotypes in the chicken, where most other pigmentation variants influence feather color and patterning. The Silkie chicken is the most widespread and well-studied breed displaying this phenotype. The presence of the domin...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002412
更新日期:2011-12-01 00:00:00
abstract::Cellular adaptation to stress is essential to ensure organismal survival. NRF2/NFE2L2 is a key determinant of xenobiotic stress responses, and loss of negative regulation by the KEAP1-CUL3 proteasome system is implicated in several chemo- and radiation-resistant cancers. Advantageously using C. elegans alongside human...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006762
更新日期:2017-04-28 00:00:00
abstract::DNA mismatch repair greatly increases genome fidelity by recognizing and removing replication errors. In order to understand how this fidelity is maintained, it is important to uncover the relative specificities of the different components of mismatch repair. There are two major mispair recognition complexes in eukary...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003920
更新日期:2013-10-01 00:00:00
abstract::Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). Rare genetic mutations in genes such as Parkin, Pink1, DJ-1, α-synuclein, LRRK2 and GBA are found to be responsible for the disease in about 15% of the cases. A key u...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008352
更新日期:2019-08-26 00:00:00
abstract::The genetic architecture of the small and isolated Greenlandic population is advantageous for identification of novel genetic variants associated with cardio-metabolic traits. We aimed to identify genetic loci associated with body mass index (BMI), to expand the knowledge of the genetic and biological mechanisms under...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008544
更新日期:2020-01-24 00:00:00
abstract::DNA interstrand crosslinks (ICLs) are among the most toxic types of damage to a cell. For this reason, many ICL-inducing agents are effective therapeutic agents. For example, cisplatin and nitrogen mustards are used for treating cancer and psoralen plus UVA (PUVA) is useful for treating psoriasis. However, repair mech...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000189
更新日期:2008-09-12 00:00:00
abstract::Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant disease with high penetrance, manifest by brain hemorrhages in young normotensive adults. In Iceland, this condition is caused by the L68Q mutation in the cystatin C gene, with contemporary carriers reaching an average age of only 30 years. Here...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000099
更新日期:2008-06-20 00:00:00
abstract::The deregulation of metabolism is a hallmark of aging. As such, changes in the expression of metabolic genes and the profiles of amino acid levels are features associated with aging animals. We previously reported that the levels of most amino acids decline with age in Caenorhabditis elegans (C. elegans). Glycine, in ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007633
更新日期:2019-03-07 00:00:00
abstract::Rheumatoid arthritis is a chronic inflammatory disease with a high prevalence and substantial socioeconomic burden. Despite intense research efforts, its aetiology and pathogenesis remain poorly understood. To identify novel genes and/or cellular pathways involved in the pathogenesis of the disease, we utilized a well...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0010048
更新日期:2005-10-01 00:00:00
abstract::The Core Binding Factor (CBF) protein RUNX1 is a master regulator of definitive hematopoiesis, crucial for hematopoietic stem cell (HSC) emergence during ontogeny. RUNX1 also plays vital roles in adult mice, in regulating the correct specification of numerous blood lineages. Akin to the other mammalian Runx genes, Run...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005814
更新日期:2016-01-25 00:00:00
abstract::The epigenetic regulation of gene expression by the covalent modification of histones is a fundamental mechanism required for the proper differentiation of germ line cells during development. Trimethylation of histone 3 lysine 9 (H3K9me3) leads to chromatin silencing and the formation of heterochromatin by recruitment...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000644
更新日期:2009-09-01 00:00:00
abstract::The conserved protein kinase Sch9 is a central player in the nutrient-induced signaling network in yeast, although only few of its direct substrates are known. We now provide evidence that Sch9 controls the vacuolar proton pump (V-ATPase) to maintain cellular pH homeostasis and ageing. A synthetic sick phenotype arise...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006835
更新日期:2017-06-12 00:00:00
abstract::For many decades, Salmonella enterica has been subdivided by serological properties into serovars or further subdivided for epidemiological tracing by a variety of diagnostic tests with higher resolution. Recently, it has been proposed that so-called eBurst groups (eBGs) based on the alleles of seven housekeeping gene...
journal_title:PLoS genetics
pub_type: 杂志文章,评审
doi:10.1371/journal.pgen.1007261
更新日期:2018-04-05 00:00:00
abstract::Numerous lines of evidence point to a genetic basis for facial morphology in humans, yet little is known about how specific genetic variants relate to the phenotypic expression of many common facial features. We conducted genome-wide association meta-analyses of 20 quantitative facial measurements derived from the 3D ...
journal_title:PLoS genetics
pub_type: 杂志文章,meta分析
doi:10.1371/journal.pgen.1006149
更新日期:2016-08-25 00:00:00
abstract::Selenium is an important trace element that occurs in proteins in the form of selenocysteine (Sec) and in tRNAs in the form of selenouridine. Recent large-scale metagenomics projects provide an opportunity for understanding global trends in trace element utilization. Herein, we characterized the selenoproteome of the ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000095
更新日期:2008-06-13 00:00:00
abstract::In nature, microbes often need to "decide" which of several available nutrients to utilize, a choice that depends on a cell's inherent preference and external nutrient levels. While natural environments can have mixtures of different nutrients, phenotypic variation in microbes' decisions of which nutrient to utilize i...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006766
更新日期:2017-05-24 00:00:00
abstract::Evolutionary outcomes depend not only on the selective forces acting upon a species, but also on the genetic background. However, large timescales and uncertain historical selection pressures can make it difficult to discern such important background differences between species. Experimental evolution is one tool to c...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006585
更新日期:2017-02-14 00:00:00
abstract::Iran, despite its size, geographic location and past cultural influence, has largely been a blind spot for human population genetic studies. With only sparse genetic information on the Iranian population available, we pursued its genome-wide and geographic characterization based on 1021 samples from eleven ethnic grou...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008385
更新日期:2019-09-24 00:00:00
abstract::Increases in fruit weight of cultivated vegetables and fruits accompanied the domestication of these crops. Here we report on the positional cloning of a quantitative trait locus (QTL) controlling fruit weight in tomato. The derived allele of Cell Size Regulator (CSR-D) increases fruit weight predominantly through enl...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006930
更新日期:2017-08-17 00:00:00
abstract::The integration of expression profiling with linkage analysis has increasingly been used to identify genes underlying complex phenotypes. The effects of gender on the regulation of many physiological traits are well documented; however, "genetical genomic" analyses have not yet addressed the degree to which their conc...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0020015
更新日期:2006-02-01 00:00:00