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81.
Here we present a biochemical and molecular biology study of the enzyme pyruvate kinase (PYK) from the parasitic protozoa Leishmania donovani. The PYK gene was cloned, mutagenised and over expressed and its kinetic parameters determined. Like in other kinetoplastids, L. donovani PYK is allosterically stimulated by the effector fructose 2,6 biphosphate and not by fructose 1,6 biphosphate. When the putative effector binding site of L. donovani PYK was mutagenised, we obtained two mutants with extreme kinetic behavior: Lys453Leu, which retained a sigmoidal kinetics and was little affected by the effector; and His480Gln, which deployed a hyperbolic kinetics that was not changed by the addition of the effector. Molecular Dynamics (MD) studies revealed that the mutations not only altered the effector binding site of L. donovani PYK but also changed the folding of its domain C. 相似文献
82.
Arturo Andrade Alejandro Sandoval Ricardo Gonzlez-Ramírez Diane Lipscombe Kevin P. Campbell Ricardo Felix 《Cell calcium》2009,46(4):282-292
The auxiliary CaVα2δ-1 subunit is an important component of voltage-gated Ca2+ (CaV) channel complexes in many tissues and of great interest as a drug target. Nevertheless, its exact role in specific cell functions is still unknown. This is particularly important in the case of the neuronal L-type CaV channels where these proteins play a key role in the secretion of neurotransmitters and hormones, gene expression, and the activation of other ion channels. Therefore, using a combined approach of patch-clamp recordings and molecular biology, we studied the role of the CaVα2δ-1 subunit on the functional expression and the pharmacology of recombinant L-type CaV1.3 channels in HEK-293 cells. Co-expression of CaVα2δ-1 significantly increased macroscopic currents and conferred the CaV1.3α1/CaVβ3 channels sensitivity to the antiepileptic/analgesic drugs gabapentin and AdGABA. In contrast, CaVα2δ-1 subunits harboring point mutations in N-glycosylation consensus sequences or the proteolytic site as well as in conserved cysteines in the transmembrane δ domain of the protein, reduced functionality in terms of enhancement of CaV1.3α1/CaVβ3 currents. In addition, co-expression of the δ domain drastically inhibited macroscopic currents through recombinant CaV1.3 channels possibly by affecting channel synthesis. Together these results provide several lines of evidence that the CaVα2δ-1 auxiliary subunit may interact with CaV1.3 channels and regulate their functional expression. 相似文献
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85.
Lalioti VS Vergarajauregui S Tsuchiya Y Hernandez-Tiedra S Sandoval IV 《Journal of cellular physiology》2009,218(2):416-426
We have previously reported the physical interaction between Daxx, the adaptor protein that mediates activation of the Jun amino-terminal kinase (JNK), and GLUT4, the insulin-dependent glucose transporter, interaction that involves their C-domains. Co-immunoprecipitation and two-hybrid-based protein-protein interaction studies show now that Daxx and GLUT4 interact with JNK1 through D-sites in their NH(2)-(aa 1-501) and large endofacial loop, respectively. Serum deprivation strongly enhances the association of JNK1 with Daxx and dissociates the kinase from GLUT4. SP600125, a potent JNK1 inhibitor, reduces the JNK1 activity associated with GLUT4 and the phosphorylation of two minor GLUT4 species in serum-starved 3T3-L1 adipocytes. In addition, Daxx interacts with kinesin KIF5B through the 6xTPR domain of the kinesin light chain, a domain engaged in the grab hold of protein cargo by kinesin motors that codistribute with JNK. Depletion of Daxx in 3T3-L1 adipocytes provokes the partial translocation of the GLUT4 retained in the GLUT4 storage compartment to endosomes. 相似文献
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87.
Kevin D. Lafferty Darcie Goodman Cristina P. Sandoval 《Biodiversity and Conservation》2006,15(7):2217-2230
Promoting recreation and preserving wildlife are often dual missions for land managers, yet recreation may impact wildlife.
Because individual disturbances are seemingly inconsequential, it is difficult to convince the public that there is a conservation
value to restricting recreation to reduce disturbance. We studied threatened western snowy plovers (Charadrius alexandrinus nivosus) at a public beach (Sands Beach, Coal Oil Point Reserve) in Santa Barbara, California (USA) before and during a period when
a barrier directed foot traffic away from a section of upper beach where snowy plovers roost. The barrier reduced disturbance
rates by more than half. Snowy plovers increased in abundance (throughout the season) and their distribution contracted to
within the protected area. Snowy plovers that were outside the protected area in the morning moved inside as people began
using the beach. Experiments with quail eggs indicated an 8% daily risk of nest trampling outside the protected area. Before
protection, plovers did not breed at Coal Oil Point. During protection, snowy plovers bred in increasing numbers each year
and had high success at fledging young. These results demonstrate how recreational disturbance can degrade habitat for shorebirds
and that protecting quality habitat may have large benefits for wildlife and small impacts to recreation. 相似文献
88.
Jingyu Diao Rie Komura Tatsuya Sano Homer Pantua Kelly M. Storek Hiroko Inaba Haruhiko Ogawa Cameron L. Noland Yutian Peng Susan L. Gloor Donghong Yan Jing Kang Anand Kumar Katakam Michael Volny Peter Liu Nicholas N. Nickerson Wendy Sandoval Cary D. Austin Jeremy Murray Steven T. Rutherford Mike Reichelt Yiming Xu Min Xu Hayato Yanagida Junichi Nishikawa Patrick C. Reid Christian N. Cunningham Sharookh B. Kapadia 《Journal of bacteriology》2021,203(13)
89.
Erika Chavira-Suárez Alejandro Sandoval Ricardo Felix Mónica Lamas 《Biochemical and biophysical research communications》2011,404(2):678
Normal vision depends on the correct function of retinal neurons and glia and it is impaired in the course of diabetic retinopathy. Müller cells, the main glial cells of the retina, suffer morphological and functional alterations during diabetes participating in the pathological retinal dysfunction. Recently, we showed that Müller cells express the pleiotropic protein potassium channel interacting protein 3 (KChIP3), an integral component of the voltage-gated K+ channels KV4. Here, we sought to analyze the role of KChIP3 in the molecular mechanisms underlying hyperglycemia-induced phenotypic changes in the glial elements of the retina. The expression and function of KChIp3 was analyzed in vitro in rat Müller primary cultures grown under control (5.6 mM) or high glucose (25 mM) (diabetic-like) conditions. We show the up-regulation of KChIP3 expression in Müller cell cultures under high glucose conditions and demonstrate a previously unknown interaction between the KV4 channel and KChIP3 in Müller cells. We show evidence for the expression of a 4-AP-sensitive transient outward voltage-gated K+ current and an alteration in the inactivation of the macroscopic outward K+ currents expressed in high glucose-cultured Müller cells. Our data support the notion that induction of KChIP3 and functional changes of KV4 channels in Müller cells could exert a physiological role in the onset of diabetic retinopathy. 相似文献
90.
Wilson DG Phamluong K Li L Sun M Cao TC Liu PS Modrusan Z Sandoval WN Rangell L Carano RA Peterson AS Solloway MJ 《The Journal of cell biology》2011,193(5):935-951
Melanoma inhibitory activity member 3 (MIA3/TANGO1) [corrected] is an evolutionarily conserved endoplasmic reticulum resident transmembrane protein. Recent in vitro studies have shown that it is required for the loading of collagen VII, but not collagen I, into COPII-coated transport vesicles. In this paper, we show that mice lacking Mia3 are defective for the secretion of numerous collagens, including collagens I, II, III, IV, VII, and IX, from chondrocytes, fibroblasts, endothelial cells, and mural cells. Collagen deposition by these cell types is abnormal, and extracellular matrix composition is compromised. These changes are associated with intracellular accumulation of collagen and the induction of a strong unfolded protein response, primarily within the developing skeleton. Chondrocyte maturation and bone mineralization are severely compromised in Mia3-null embryos, leading to dwarfism and neonatal lethality. Thus, Mia3's role in protein secretion is much broader than previously realized, and it may, in fact, be required for the efficient secretion of all collagen molecules in higher organisms. 相似文献