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1.
Mol Psychiatry ; 28(3): 1351-1364, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36434054

RESUMEN

Spatial learning and memory flexibility are known to require long-term potentiation (LTP) and long-term depression (LTD), respectively, on a cellular basis. We previously showed that cyclin Y (CCNY), a synapse-remodeling cyclin, is a novel actin-binding protein and an inhibitory regulator of functional and structural LTP in vitro. In this study, we report that Ccny knockout (KO) mice exhibit enhanced LTP and weak LTD at Schaffer collateral-CA1 synapses in the hippocampus. In accordance with enhanced LTP, Ccny KO mice showed improved spatial learning and memory. However, although previous studies reported that normal LTD is necessary for memory flexibility, Ccny KO mice intriguingly showed improved memory flexibility, suggesting that weak LTD could exert memory flexibility when combined with enhanced LTP. At the molecular level, CCNY modulated spatial learning and memory flexibility by distinctively affecting the cofilin-actin signaling pathway in the hippocampus. Specifically, CCNY inhibited cofilin activation by original learning, but reversed such inhibition by reversal learning. Furthermore, viral-mediated overexpression of a phosphomimetic cofilin-S3E in hippocampal CA1 regions enhanced LTP, weakened LTD, and improved spatial learning and memory flexibility, thus mirroring the phenotype of Ccny KO mice. In contrast, the overexpression of a non-phosphorylatable cofilin-S3A in hippocampal CA1 regions of Ccny KO mice reversed the synaptic plasticity, spatial learning, and memory flexibility phenotypes observed in Ccny KO mice. Altogether, our findings demonstrate that LTP and LTD cooperatively regulate memory flexibility. Moreover, CCNY suppresses LTP while facilitating LTD in the hippocampus and negatively regulates spatial learning and memory flexibility through the control of cofilin-actin signaling, proposing CCNY as a learning regulator modulating both memorizing and forgetting processes.


Asunto(s)
Actinas , Aprendizaje Espacial , Ratones , Animales , Hipocampo/metabolismo , Potenciación a Largo Plazo/fisiología , Plasticidad Neuronal/fisiología , Sinapsis/metabolismo , Ratones Noqueados , Ciclinas/genética , Ciclinas/metabolismo , Factores Despolimerizantes de la Actina/metabolismo
2.
Int J Mol Sci ; 19(11)2018 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-30428563

RESUMEN

Lymphatic filariasis and onchocerciasis caused by filarial nematodes are important diseases leading to considerable morbidity throughout tropical countries. Diethylcarbamazine (DEC), albendazole (ALB), and ivermectin (IVM) used in massive drug administration are not highly effective in killing the long-lived adult worms, and there is demand for the development of novel macrofilaricidal drugs affecting new molecular targets. A Ca2+ binding protein, calumenin, was identified as a novel and nematode-specific drug target for filariasis, due to its involvement in fertility and cuticle development in nematodes. As sterilizing and killing effects of the adult worms are considered to be ideal profiles of new drugs, calumenin could be an eligible drug target. Indeed, the Caenorhabditis elegans mutant model of calumenin exhibited enhanced drug acceptability to both microfilaricidal drugs (ALB and IVM) even at the adult stage, proving the roles of the nematode cuticle in efficient drug entry. Molecular modeling revealed that structural features of calumenin were only conserved among nematodes (C. elegans, Brugia malayi, and Onchocerca volvulus). Structural conservation and the specificity of nematode calumenins enabled the development of drugs with good target selectivity between parasites and human hosts. Structure-based virtual screening resulted in the discovery of itraconazole (ITC), an inhibitor of sterol biosynthesis, as a nematode calumenin-targeting ligand. The inhibitory potential of ITC was tested using a nematode mutant model of calumenin.


Asunto(s)
Antinematodos/química , Antinematodos/farmacología , Descubrimiento de Drogas , Albendazol/química , Albendazol/farmacología , Albendazol/uso terapéutico , Secuencia de Aminoácidos , Animales , Antinematodos/uso terapéutico , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/química , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Unión al Calcio/química , Proteínas de Unión al Calcio/metabolismo , Dietilcarbamazina/química , Dietilcarbamazina/farmacología , Dietilcarbamazina/uso terapéutico , Evaluación Preclínica de Medicamentos , Filariasis/tratamiento farmacológico , Itraconazol/química , Itraconazol/farmacología , Itraconazol/uso terapéutico , Ivermectina/química , Ivermectina/farmacología , Ivermectina/uso terapéutico , Modelos Moleculares , Relación Estructura-Actividad Cuantitativa
3.
Int Neurourol J ; 26(4): 275-287, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36599336

RESUMEN

Human endogenous retroviruses (HERVs) are originated from ancient exogenous retroviruses, which infected human germ line cells millions of years ago. HERVs have generally lost their replication and retrotransposition abilities, but adopted physiological roles in human biology. Though mostly inactive, HERVs can be reactivated by internal and external factors such as inflammations and environmental conditions. Their aberrant expression can participate in various human malignancies with complex etiology. This review describes the features and functions of HERVs in urological subjects, such as urological cancers and human reproduction. It provides the current knowledge of the HERVs and useful insights helping practice in urology clinics.

4.
Anim Cells Syst (Seoul) ; 26(5): 223-231, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36275448

RESUMEN

To support life, the osmolality of the cellular fluid is tightly regulated by various means, including osmolyte control. Dicarbonyl/L-xylulose reductase (DCXR) is a highly conserved enzyme reducing L-xylulose to xylitol, which serves as an effective osmolyte in various mammalian and human tissues such as lung epithelium, sperm, and lens. DHS-21 is the only DCXR ortholog in Caenorhabditis elegans, and DCXR null mutant worms accumulate eggs in the uterus. However, it has been unknown how and why the mutant worms impair egg retention. In this study, we tested whether the egg-retention in dhs-21 (jh129), the DCXR null mutant worm, is sensitive to changes in osmolarity. Low osmolality reverted the egg retention phenotype of dhs-21(jh129), while high osmolarity aggravated it. Also, knock-down of either one of osr-1, osm-7, or osm-11, osmoregulatory genes, also rescued egg-retention phenotypes of the null mutants. The study indicates that DCXR functions in fluid homeostasis by regulating cellular osmolality in C. elegans and provides insights into DCXR-involved clinical conditions, such as congenital cataracts and malfunctioning lung and kidney.

5.
Biochim Biophys Acta ; 1797(10): 1687-95, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20637717

RESUMEN

Vacuolar (H(+))-ATPases, also called V-ATPases, are ATP-driven proton pumps that are highly phylogenetically conserved. Early biochemical and cell biological studies have revealed many details of the molecular mechanism of proton pumping and of the structure of the multi-subunit membrane complex, including the stoichiometry of subunit composition. In addition, yeast and mouse genetics have broadened our understanding of the physiological consequences of defective vacuolar acidification and its related disease etiologies. Recently, phenotypic investigation of V-ATPase mutants in Caenorhabditis elegans has revealed unexpected new roles of V-ATPases in both cellular function and early development. In this review, we discuss the functions of the V-ATPases discovered in C. elegans.


Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/enzimología , Bombas de Protones/metabolismo , ATPasas de Translocación de Protón Vacuolares/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Sitios de Unión , Caenorhabditis elegans/embriología , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Regulación del Desarrollo de la Expresión Génica , Mutación , Subunidades de Proteína/genética , Subunidades de Proteína/metabolismo , ATPasas de Translocación de Protón Vacuolares/genética
6.
Anim Cells Syst (Seoul) ; 25(6): 358-368, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35059135

RESUMEN

Human endogenous retroviruses (HERVs) are 'fossil viruses' that resulted from stable integrations of exogenous retroviruses throughout evolution. HERVs are defective and do not produce infectious viral particles. However, some HERVs retain a limited coding capacity and produce retroviral transcripts and proteins, which function in human developmental process and various pathologies, including many cancers and neurological diseases. Recently, it has been reported that HERVs are differently expressed in COVID-19 disease caused by infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this review, we discuss the molecular structure and function of HERV ENV proteins, particularly syncytins, and their conventional roles in human development and diseases, and potential involvement in COVID-19 regarding the newly reported mental symptoms. We also address COVID-19 vaccine-related infertility concerns arising from the similarity of syncytin with the spike protein of SARS-CoV-2, which have been proved invalid.

7.
Mol Cells ; 44(12): 861-878, 2021 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-34963103

RESUMEN

The human genome contains many retroviral elements called human endogenous retroviruses (HERVs), resulting from the integration of retroviruses throughout evolution. HERVs once were considered inactive junk because they are not replication-competent, primarily localized in the heterochromatin, and silenced by methylation. But HERVs are now clearly shown to actively regulate gene expression in various physiological and pathological conditions such as developmental processes, immune regulation, cancers, autoimmune diseases, and neurological disorders. Recent studies report that HERVs are activated in patients suffering from coronavirus disease 2019 (COVID-19), the current pandemic caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. In this review, we describe internal and external factors that influence HERV activities. We also present evidence showing the gene regulatory activity of HERV LTRs (long terminal repeats) in model organisms such as mice, rats, zebrafish, and invertebrate models of worms and flies. Finally, we discuss several molecular and cellular pathways involving various transcription factors and receptors, through which HERVs affect downstream cellular and physiological events such as epigenetic modifications, calcium influx, protein phosphorylation, and cytokine release. Understanding how HERVs participate in various physiological and pathological processes will help develop a strategy to generate effective therapeutic approaches targeting HERVs.


Asunto(s)
Enfermedades Autoinmunes/genética , Retrovirus Endógenos/genética , Regulación de la Expresión Génica , Modelos Animales , Neoplasias/genética , Secuencias Repetidas Terminales/genética , Animales , Enfermedades Autoinmunes/virología , COVID-19/genética , COVID-19/virología , Humanos , Neoplasias/virología , SARS-CoV-2/fisiología
8.
Mol Cells ; 44(3): 160-167, 2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33692220

RESUMEN

The determinant factors of an organism's size during animal development have been explored from various angles but remain partially understood. In Caenorhabditis elegans, many genes affecting cuticle structure, cell growth, and proliferation have been identified to regulate the worm's overall morphology, including body size. While various mutations in those genes directly result in changes in the morphological phenotypes, there is still a need for established, clear, and distinct standards to determine the apparent abnormality in a worm's size and shape. In this study, we measured the body length, body width, terminal bulb length, and head size of mutant worms with reported Dumpy (Dpy), Small (Sma) or Long (Lon) phenotypes by plotting and comparing their respective ratios of various parameters. These results show that the Sma phenotypes are proportionally smaller overall with mild stoutness, and Dpy phenotypes are significantly stouter and have disproportionally small head size. This study provides a standard platform for determining morphological phenotypes designating and annotating mutants that exhibit body shape variations, defining the morphological phenotype of previously unexamined mutants.


Asunto(s)
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/genética , Animales , Fenotipo
9.
BMC Cell Biol ; 11: 9, 2010 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-20100334

RESUMEN

BACKGROUND: Caspases are cysteine proteases with essential functions in the apoptotic pathway; their proteolytic activity toward various substrates is associated with the morphological changes of cells. Recent reports have described non-apoptotic functions of caspases, including autophagy. In this report, we searched for novel modifiers of the phenotype of Dcp-1 gain-of-function (GF) animals by screening promoter element- inserted Drosophila melanogaster lines (EP lines). RESULTS: We screened approximately 15,000 EP lines and identified 72 Dcp-1-interacting genes that were classified into 10 groups based on their functions and pathways: 4 apoptosis signaling genes, 10 autophagy genes, 5 insulin/IGF and TOR signaling pathway genes, 6 MAP kinase and JNK signaling pathway genes, 4 ecdysone signaling genes, 6 ubiquitination genes, 11 various developmental signaling genes, 12 transcription factors, 3 translation factors, and 11 other unclassified genes including 5 functionally undefined genes. Among them, insulin/IGF and TOR signaling pathway, MAP kinase and JNK signaling pathway, and ecdysone signaling are known to be involved in autophagy. Together with the identification of autophagy genes, the results of our screen suggest that autophagy counteracts Dcp-1-induced apoptosis. Consistent with this idea, we show that expression of eGFP-Atg5 rescued the eye phenotype caused by Dcp-1 GF. Paradoxically, we found that over-expression of full-length Dcp-1 induced autophagy, as Atg8b-GFP, an indicator of autophagy, was increased in the eye imaginal discs and in the S2 cell line. Taken together, these data suggest that autophagy suppresses Dcp-1-mediated apoptotic cell death, whereas Dcp-1 positively regulates autophagy, possibly through feedback regulation. CONCLUSIONS: We identified a number of Dcp-1 modifiers that genetically interact with Dcp-1-induced cell death. Our results showing that Dcp-1 and autophagy-related genes influence each other will aid future investigations of the complicated relationships between apoptosis and autophagy.


Asunto(s)
Autofagia , Caspasas/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/enzimología , Animales , Apoptosis , Caspasas/genética , Línea Celular , Proteínas de Drosophila/genética , Ojo/metabolismo , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Fenotipo , Transducción de Señal
10.
Mol Cells ; 43(8): 671-685, 2020 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-32576715

RESUMEN

The regulator of calcineurin (RCAN) was first reported as a novel gene called DSCR1, encoded in a region termed the Down syndrome critical region (DSCR) of human chromosome 21. Genome sequence comparisons across species using bioinformatics revealed three members of the RCAN gene family, RCAN1, RCAN2, and RCAN3, present in most jawed vertebrates, with one member observed in most invertebrates and fungi. RCAN is most highly expressed in brain and striated muscles, but expression has been reported in many other tissues, as well, including the heart and kidneys. Expression levels of RCAN homologs are responsive to external stressors such as reactive oxygen species, Ca2+, amyloid ß, and hormonal changes and upregulated in pathological conditions, including Alzheimer's disease, cardiac hypertrophy, diabetes, and degenerative neuropathy. RCAN binding to calcineurin, a Ca2+/calmodulin-dependent phosphatase, inhibits calcineurin activity, thereby regulating different physiological events via dephosphorylation of important substrates. Novel functions of RCANs have recently emerged, indicating involvement in mitochondria homeostasis, RNA binding, circadian rhythms, obesity, and thermogenesis, some of which are calcineurin-independent. These developments suggest that besides significant contributions to DS pathologies and calcineurin regulation, RCAN is an important participant across physiological systems, suggesting it as a favorable therapeutic target.


Asunto(s)
Calcineurina/metabolismo , Síndrome de Down/metabolismo , Humanos
11.
BMB Rep ; 53(10): 521-526, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32867919

RESUMEN

Endogenous retroviruses (ERVs) are retrotransposons present in various metazoan genomes and have been implicated in metazoan evolution as well as in nematodes and humans. The long terminal repeat (LTR) retrotransposons contain several regulatory sequences including promoters and enhancers that regulate endogenous gene expression and thereby control organismal development and response to environmental change. ERVs including the LTR retrotransposons constitute 8% of the human genome and less than 0.6% of the Caenorhabditis elegans (C. elegans) genome, a nematode genetic model system. To investigate the evolutionarily conserved mechanism behind the transcriptional activity of retrotransposons, we generated a transgenic worm model driving green fluorescent protein (GFP) expression using Human endogenous retroviruses (HERV)-K LTR as a promoter. The promoter activity of HERV-K LTR was robust and fluorescence was observed in various tissues throughout the developmental process. Interestingly, persistent GFP expression was specifically detected in the adult vulva muscle. Using deletion constructs, we found that the region from positions 675 to 868 containing the TATA box was necessary for promoter activity driving gene expression in the vulva. Interestingly, we found that the promoter activity of the LTR was dependent on che-1 transcription factor, a sensory neuron driver, and lin-15b, a negative regulator of RNAi and germline gene expression. These results suggest evolutionary conservation of the LTR retrotransposon activity in transcriptional regulation as well as the possibility of che-1 function in non-neuronal tissues. [BMB Reports 2020; 53(10): 521-526].


Asunto(s)
Retrovirus Endógenos/genética , Regulación de la Expresión Génica/genética , Regiones Promotoras Genéticas/genética , Animales , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Retrovirus Endógenos/metabolismo , Expresión Génica/genética , Retroelementos/genética , Secuencias Repetidas Terminales/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Transcripción Genética/genética
12.
Biochem Biophys Res Commun ; 390(1): 136-41, 2009 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-19785996

RESUMEN

Nramp1 (natural resistance-associated macrophage protein-1) is a functionally conserved iron-manganese transporter in macrophages. Manganese (Mn), a superoxide scavenger, is required in trace amounts and functions as a cofactor for most antioxidants. Three Nramp homologs, smf-1, smf-2, and smf-3, have been identified thus far in the nematode Caenorhabditis elegans. A GFP promoter assay revealed largely intestinal expression of the smf genes from early embryonic through adult stages. In addition, smf deletion mutants showed increased sensitivity to excess Mn and mild sensitivity to EDTA. Interestingly, these smf deletion mutants demonstrated hypersensitivity to the pathogen Staphylococcus aureus, an effect that was rescued by Mn feeding or knockdown of the Golgi calcium/manganese ATPase, pmr-1, indicating that Mn uptake is essential for the innate immune system. This reversal of pathogen sensitivity by Mn feeding suggests a protective and therapeutic role of Mn in pathogen evasion systems. We propose that the C. elegans intestinal lumen may mimic the mammalian macrophage phagosome and thus could be a simple model for studying Mn-mediated innate immunity.


Asunto(s)
Caenorhabditis elegans/metabolismo , Proteínas de Transporte de Catión/metabolismo , Mucosa Intestinal/metabolismo , Manganeso/metabolismo , Animales , Caenorhabditis elegans/genética , Caenorhabditis elegans/microbiología , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , ATPasas Transportadoras de Calcio/genética , ATPasas Transportadoras de Calcio/metabolismo , Proteínas de Transporte de Catión/genética , Ácido Edético/farmacología , Técnicas de Silenciamiento del Gen , Inmunidad Innata , Staphylococcus aureus
13.
Anim Cells Syst (Seoul) ; 23(6): 399-406, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31853377

RESUMEN

Phosphorylation is one of the critical protein modifications, which can lead to changing the activity of the proteins and regulating a variety of biological processes. Therefore, it is essential to properly maintain the phosphorylation level on proteins by balancing the activity of kinases and phosphatases. In this study, we report that calcineurin, a serine/threonine phosphatase, counteracts with a salt inducible kinase (SIK) to control male tail development in Caenorhabditis elegans. The counteracting regulation is cell lineage-dependent; the number of defective rays from T lineage in animals lacking calcineurin tax-6 is decreased by knock-down of SIK kin-29. This result is in contrast with the knock-down of bone marrow protein (BMP) receptor kinase sma-6, which slightly aggravates the T lineage defect. Also, sma-6 knock-down results in modest defect in ray 1 of V5 lineage in the absence of tax-6 activity. Finally, knock-down of a tyrosine phosphatase cdc-25.3 does not affect the defective ray phenotype of calcineurin tax-6 loss-of-function(lf) mutants. Altogether, these results suggest that balanced phosphorylation mediated by tax-6 and kin-29 is required for proper development of T lineage rays, and tax-6 and sma-6 may function in a parallel pathway in the developmental process of V5 lineage ray 1. This study emphasizes the elaborated developmental process of male ray formation, in which carefully coordinated expression of various genes is essential.

14.
Mol Cells ; 47(3): 100009, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38211721
15.
J Mol Biol ; 372(2): 331-40, 2007 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-17651753

RESUMEN

Accumulation of unfolded proteins in the endoplasmic reticulum triggers the unfolded protein response (UPR) pathway, which increases the expression of chaperones to maintain the homeostasis. Calreticulin is a calcium-binding chaperone located in the lumen of endoplasmic reticulum (ER). Here we show that in response to a UPR inducing reagent, tunicamycin, the expression of calreticulin (crt-1) is specifically up-regulated in Caenorhabditis elegans. Tunicamycin (TM) induced expression of the crt-1 requires IRE-1 and XBP-1 but is ATF-6 and PEK-1 independent. Analysis of the crt-1 promoter reveals a putative XBP-1 binding site at the -284 to -278 bp region, which was shown to be necessary for TM-mediated induction. Genetic analysis of crt-1 mutants and mutants of UPR pathway genes show various degrees of developmental arrest upon TM treatment. Our results suggest that the TM-induced UPR pathway culminates in the up-regulation of crt-1, which protects the worm from deleterious accumulation of unfolded proteins in the ER. Knockdown of the crt-1, pdi-2, or pdi-3 increased the crt-1 expression, whereas knockdown of the hsp-3 or hsp-4 did not have any effect on crt-1 expression, indicating the existence of complex compensatory networks to cope up with ER stress.


Asunto(s)
Caenorhabditis elegans/metabolismo , Calreticulina/metabolismo , Retículo Endoplásmico/metabolismo , Regulación de la Expresión Génica , Pliegue de Proteína , Animales , Caenorhabditis elegans/citología , Caenorhabditis elegans/efectos de los fármacos , Calreticulina/genética , Retículo Endoplásmico/efectos de los fármacos , Retroalimentación Fisiológica , Regulación de la Expresión Génica/efectos de los fármacos , Proteínas de Choque Térmico/deficiencia , Proteínas de Choque Térmico/metabolismo , Mutación/genética , Desnaturalización Proteica , Proteína Disulfuro Isomerasas/deficiencia , Proteína Disulfuro Isomerasas/metabolismo , Elementos de Respuesta/genética , Tunicamicina/farmacología , Regulación hacia Arriba/efectos de los fármacos
16.
Mol Cells ; 25(1): 50-4, 2008 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-18319613
17.
Mol Cells ; 25(4): 566-71, 2008 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-18460897

RESUMEN

Calcineurin (Cn) is a calcium/calmodulin-dependent serine/threonine protein phosphatase that has diverse functions in different cell types and organisms. We screened proteins interacting with the C. elegans CnA homolog, TAX-6, by the yeast two-hybrid system. CNP-3 (Calcineurin interacting protein-3) is a novel protein that physically interacts with the catalytic domain of TAX-6. It is strongly expressed in the nuclei of intestine, hypodermis, dorsal uterine regions and spermatheca. Expression begins around the 60-cell stage and proceeds during all larval stages and the adult. To elucidate the biological function of cnp-3 we isolated a cnp-3 deletion mutant. Since CNP-3 binds CnA, we looked at factors associated with calcineurin loss-of-function mutants, such as brood size, body size, serotonin- and levamisole-mediated egg-laying behavior. The cnp-3(jh145) single mutant had no gross defects compared to wild-type animal. However, the phenotypes of the double mutants, tax-6(p675);cnp-3(jh145) and cnb-1(jh103);cnp-3(jh145), were more severe in terms of brood size, body size and serotonin-mediated egg-laying defects than tax-6(p675) and cnb-1(jh103), respectively. These results suggest that dysfunction of cnp-3 enhances certain calcineurin loss-of-function phenotypes in C. elegans.


Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Calcineurina/metabolismo , Proteínas Portadoras/metabolismo , Animales , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/genética , Calcineurina/genética , Calmodulina/metabolismo , Proteínas Portadoras/genética , Clonación Molecular , Organismos Modificados Genéticamente/genética , Organismos Modificados Genéticamente/metabolismo , Unión Proteica/genética , Eliminación de Secuencia , Transducción de Señal/genética , Técnicas del Sistema de Dos Híbridos
19.
FEBS Lett ; 581(28): 5445-53, 2007 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-17981157

RESUMEN

Inorganic pyrophosphatase (PPase) catalyzes the hydrolysis of inorganic pyrophosphate (PPi) into phosphate (Pi), which provides a thermodynamic driving force for important biosynthetic reactions. The nematode Caenorhabditis elegans gene C47E12.4 encodes a PPase (PYP-1) which shows 54% amino acid identity with human PPase. PYP-1 exhibits specific enzyme activity and is mainly expressed in the intestinal and nervous system. A null mutant of pyp-1 reveals a developmental arrest at early larval stages and exhibits gross defects in intestinal morphology and function. The larval arrest phenotype was successfully rescued by reintroduction of the pyp-1 gene, suggesting that PYP-1 is required for larval development and intestinal function in C. elegans.


Asunto(s)
Caenorhabditis elegans/crecimiento & desarrollo , Caenorhabditis elegans/metabolismo , Regulación del Desarrollo de la Expresión Génica , Regulación Enzimológica de la Expresión Génica , Pirofosfatasa Inorgánica/metabolismo , Intestinos/enzimología , Intestinos/crecimiento & desarrollo , Secuencia de Aminoácidos , Animales , Caenorhabditis elegans/genética , Secuencia Conservada , Eliminación de Gen , Humanos , Pirofosfatasa Inorgánica/química , Pirofosfatasa Inorgánica/genética , Datos de Secuencia Molecular , Mutación/genética , Fenotipo , Alineación de Secuencia
20.
Cell Commun Adhes ; 14(1): 33-43, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17453829

RESUMEN

We recently reported that SPIN90 is able to bind with several proteins involved in regulating actin cytoskeleton networks, including dynamin, WASP, beta PIX, and Nck. Based on these findings, we investigated how SPIN90 regulates the actin cytoskeleton and promotes actin assembly. This study demonstrated that aluminium fluoride-induced localization of SPIN90 to lamellipodia requires amino acids 582-722 at the SPIN90 C-terminus, which is also essential for F-actin binding and Arp2/3 complex mediated polymerization of actin into branched actin filaments. Furthermore, after deletion of the F-actin binding region (582-722 SPIN90) failed to localize at the membrane edge and was unable to promote lamellipodia formation, suggesting that the F-actin binding region in the SPIN90 C-terminus is essential for the formation of branched actin networks and regulation of the actin cytoskeleton at the leading edge of cells.


Asunto(s)
Actinas/química , Actinas/metabolismo , Proteínas Adaptadoras Transductoras de Señales/química , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Seudópodos/metabolismo , Citoesqueleto de Actina/metabolismo , Complejo 2-3 Proteico Relacionado con la Actina/metabolismo , Compuestos de Aluminio/farmacología , Línea Celular Tumoral , Fluoruros/farmacología , Humanos , Modelos Biológicos , Unión Proteica/efectos de los fármacos , Transporte de Proteínas/efectos de los fármacos , Seudópodos/química , Seudópodos/efectos de los fármacos , Fracciones Subcelulares/efectos de los fármacos , Fracciones Subcelulares/metabolismo
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