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排序方式: 共有91条查询结果,搜索用时 15 毫秒
51.
Flynn R Chen L Hameed S Spafford JD Zamponi GW 《Biochemical and biophysical research communications》2008,368(3):827-831
Rem2 belongs to the RGK family of small GTPases whose members are known to interact with the voltage gated calcium channel β subunit, and to inhibit or abolish calcium currents. To identify the underlying functional domains of Rem2, we created several N- or C-terminally truncated Rem2 proteins and examined their abilities to interact with the Cav β subunit and to regulate the activities of Cav2.2 N-type calcium channels. Confocal imaging of Rem2 in tsA-201 cells revealed that it contains a membrane-targeting signal in its C-terminus, consistent with previous studies. Co-precipitation assays showed that Cav β3 interaction depends on Rem2 residues 1-123. Only Rem2 proteins that targeted the cell membrane as well as bound the β subunit were able to reduce whole cell calcium currents. 相似文献
52.
Sefika C Mizrak Bart M Gadella Hatice Erdost Aytekin Ozer Ana MM van Pelt Federica MF van Dissel-Emiliani 《Reproductive biology and endocrinology : RB&E》2008,6(1):1-9
Background
The placenta is an important site for iron metabolism in humans. It transfers iron from the mother to the fetus. One of the major iron transport proteins is transferrin, which is a blood plasma protein crucial for iron uptake. Its localization and expression may be one of the markers to distinguish placental dysfunction.Methods
In the experimental study we used antibody preparation, mass spectrometric analysis, biochemical and immunocytochemical methods for characterization of transferrin expression on the human choriocarcinoma cell line JAR (JAR cells), placental lysates, and cryostat sections. Newly designed monoclonal antibody TRO-tf-01 to human transferrin was applied on human placentae from normal (n = 3) and abnormal (n = 9) pregnancies.Results
Variations of transferrin expression were detected in villous syncytiotrophoblast, which is in direct contact with maternal blood. In placentae from normal pregnancies, the expression of transferrin in the syncytium was significantly lower (p < 0.001) when compared to placentae from abnormal ones (gestational diabetes, pregnancy induced hypertension, drug abuse).Conclusion
These observations suggest that in the case of abnormal pregnancies, the fetus may require higher levels of transferrin in order to prevent iron depletion due to the stress from the placental dysfunction. 相似文献53.
Binding to serine 65‐phosphorylated ubiquitin primes Parkin for optimal PINK1‐dependent phosphorylation and activation 下载免费PDF全文
Agne Kazlauskaite R Julio Martínez‐Torres Scott Wilkie Atul Kumar Julien Peltier Alba Gonzalez Clare Johnson Jinwei Zhang Anthony G Hope Mark Peggie Matthias Trost Daan MF van Aalten Dario R Alessi Alan R Prescott Axel Knebel Helen Walden Miratul MK Muqit 《EMBO reports》2015,16(8):939-954
Mutations in the mitochondrial protein kinase PINK1 are associated with autosomal recessive Parkinson disease (PD). We and other groups have reported that PINK1 activates Parkin E3 ligase activity both directly via phosphorylation of Parkin serine 65 (Ser65)—which lies within its ubiquitin‐like domain (Ubl)—and indirectly through phosphorylation of ubiquitin at Ser65. How Ser65‐phosphorylated ubiquitin (ubiquitinPhospho‐Ser65) contributes to Parkin activation is currently unknown. Here, we demonstrate that ubiquitinPhospho‐Ser65 binding to Parkin dramatically increases the rate and stoichiometry of Parkin phosphorylation at Ser65 by PINK1 in vitro. Analysis of the Parkin structure, corroborated by site‐directed mutagenesis, shows that the conserved His302 and Lys151 residues play a critical role in binding of ubiquitinPhospho‐Ser65, thereby promoting Parkin Ser65 phosphorylation and activation of its E3 ligase activity in vitro. Mutation of His302 markedly inhibits Parkin Ser65 phosphorylation at the mitochondria, which is associated with a marked reduction in its E3 ligase activity following mitochondrial depolarisation. We show that the binding of ubiquitinPhospho‐Ser65 to Parkin disrupts the interaction between the Ubl domain and C‐terminal region, thereby increasing the accessibility of Parkin Ser65. Finally, purified Parkin maximally phosphorylated at Ser65 in vitro cannot be further activated by the addition of ubiquitinPhospho‐Ser65. Our results thus suggest that a major role of ubiquitinPhospho‐Ser65 is to promote PINK1‐mediated phosphorylation of Parkin at Ser65, leading to maximal activation of Parkin E3 ligase activity. His302 and Lys151 are likely to line a phospho‐Ser65‐binding pocket on the surface of Parkin that is critical for the ubiquitinPhospho‐Ser65 interaction. This study provides new mechanistic insights into Parkin activation by ubiquitinPhospho‐Ser65, which could aid in the development of Parkin activators that mimic the effect of ubiquitinPhospho‐Ser65. 相似文献
54.
BACKGROUND: An unusual case of anaplastic carcinoma of the thyroid arising from a metastatic focus of papillary carcinoma. CASE: The tumor affected a 69-year-old woman with a history of total thyroidectomy for papillary thyroid carcinoma 4 years previously. She presented with a rapidly enlarging neck mass that histologically simulated chondroblastoma. A small, embedded focus of residual follicular variant of papillary carcinoma was present. The patient died of disease 3 months later. CONCLUSION: This "chondroblastoma" variant of anaplastic thyroid carcinoma has not been reported to date. 相似文献
55.
56.
Kristina A Tendl Stefan MF Schulz Thomas P Mechtler Adele Bohn Thomas Metz Susanne Greber-Platzer David C Kasper Kurt R Herkner Chike B Item 《Epigenetics》2013,8(12):1261-1267
Diagnosis of bacterial sepsis in preterm neonates can be difficult when using serum markers that rely on physiological changes because these changes may not necessarily be the result of bacterial infections alone. This retrospective investigation explores the potential use of the DNA methylation pattern of CpG sites in the promoter region of the calcitonin-related polypeptide α (CALCA) gene as an epigenetic biomarker for bacterial sepsis in preterm newborns. Four novel changes in the DNA methylation of eight CpG sites were detected in this gene and are present only in neonates with bacterial sepsis: (1) partial methylation at -769 CpG in gram-negative or gram-positive early onset sepsis (EOS) and late onset sepsis (LOS) episodes; (2) demethylation of 8 CpGs in gram-negative EOS followed by LOS (ELS) and in gram-negative EOS; (3) demethylation of 7 CpGs in gram-positive ELS and gram-positive EOS; (4) -771 C:G > T:A; 5′ de novo -778 CpG mutation on both alleles in EOS. These changes were not detected in birth weight and gestational age matched controls or in newborns with isolated infections. Our results indicate that the DNA methylation pattern of the promoter region of the CALCA gene varies in different types of bacterial preterm sepsis, thus suggesting a potential use as an epigenetic biomarker. A prospective confirmation of these results is essential. 相似文献
57.
Valentina Taiakina Adrienne N. Boone Julia Fux Adriano Senatore Danielle Weber-Adrian J. Guy Guillemette J. David Spafford 《PloS one》2013,8(4)
NSCaTE is a short linear motif of (xWxxx(I or L)xxxx), composed of residues with a high helix-forming propensity within a mostly disordered N-terminus that is conserved in L-type calcium channels from protostome invertebrates to humans. NSCaTE is an optional, lower affinity and calcium-sensitive binding site for calmodulin (CaM) which competes for CaM binding with a more ancient, C-terminal IQ domain on L-type channels. CaM bound to N- and C- terminal tails serve as dual detectors to changing intracellular Ca2+ concentrations, promoting calcium-dependent inactivation of L-type calcium channels. NSCaTE is absent in some arthropod species, and is also lacking in vertebrate L-type isoforms, Cav1.1 and Cav1.4 channels. The pervasiveness of a methionine just downstream from NSCaTE suggests that L-type channels could generate alternative N-termini lacking NSCaTE through the choice of translational start sites. Long N-terminus with an NSCaTE motif in L-type calcium channel homolog LCav1 from pond snail Lymnaea stagnalis has a faster calcium-dependent inactivation than a shortened N-termini lacking NSCaTE. NSCaTE effects are present in low concentrations of internal buffer (0.5 mM EGTA), but disappears in high buffer conditions (10 mM EGTA). Snail and mammalian NSCaTE have an alpha-helical propensity upon binding Ca2+-CaM and can saturate both CaM N-terminal and C-terminal domains in the absence of a competing IQ motif. NSCaTE evolved in ancestors of the first animals with internal organs for promoting a more rapid, calcium-sensitive inactivation of L-type channels. 相似文献
58.
NALCN is an intriguing, orphan ion channel among the 4x6TM family of related voltage-gated cation channels, sharing a common architecture of four homologous domains consisting of six transmembrane helices, separated by three cytoplasmic linkers and delimited by N and C-terminal ends. NALCN is one of the shortest 4x6TM family members, lacking much of the variation that provides the diverse palate of gating features, and tissue specific adaptations of sodium and calcium channels. NALCN’s most distinctive feature is that that it possesses a highly adaptable pore with a calcium-like EEEE selectivity filter in radially symmetrical animals and a more sodium-like EEKE or EKEE selectivity filter in bilaterally symmetrical animals including vertebrates. Two lineages of animals evolved alternative calcium-like EEEE and sodium-like EEKE / EKEE pores, spliced to regulate NALCN functions in differing cellular environments, such as muscle (heart and skeletal) and secretory tissue (brain and glands), respectively. A highly adaptable pore in an otherwise conserved ion channel in the 4x6TM channel family is not consistent with a role for NALCN in directly gating a significant ion conductance that can be either sodium ions or calcium ions. NALCN was proposed to be an expressible Gd3+-sensitive, NMDG+-impermeant, non-selective and ohmic leak conductance in HEK-293T cells, but we were unable to distinguish these reported currents from leaky patch currents (ILP) in control HEK-293T cells. We suggest that NALCN functions as a sensor for the much larger UNC80/UNC79 complex, in a manner consistent with the coupling mechanism known for other weakly or non-conducting 4x6TM channel sensor proteins such as Nax or Cav1.1. We propose that NALCN serves as a variable sensor that responds to calcium or sodium ion flux, depending on whether the total cellular current density is generated more from calcium-selective or sodium-selective channels. 相似文献
59.
Touhidur Rahman Sonya Broughton Helen Spafford 《Entomologia Experimentalis et Applicata》2011,138(2):154-161
Western flower thrips, Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae), is a major pest of strawberry, Fragaria × ananassa Duchesne (Rosaceae). Spinosad is highly efficacious against F. occidentalis, and spinosad is believed to be compatible in an integrated pest management program. This study determined whether F. occidentalis could be controlled with predatory mites [Typhlodromips montdorensis (Schicha), Neoseiulus cucumeris (Oudemans) (both Acari: Phytoseiidae), and Hypoaspis miles (Berlese) (Acari: Laelapidae)] and spinosad in strawberry. In the glasshouse, three strawberry cultivars (Camarosa, Camino Real, and Albion) were sprayed once with spinosad at the recommended rate (80 ml 100 l?1 rate, 0.096 g a.i. l?1) or with water (control). Thrips adults were released onto plants 24 h after spraying and predatory mites released 6 days later. Spinosad significantly reduced thrips numbers compared with water. All three mite species reduced F. occidentalis numbers, and spinosad had no effect on predatory mites. Though H. miles could not be counted, the numbers of thrips in treatments with H. miles were lower than those in treatments without the mite. Thrips numbers were lowest on Camino Real and highest on Camarosa. These results suggest that the use of Camino Real with spinosad applications followed by releases of predatory mites can significantly reduce thrips numbers. 相似文献
60.