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81.
Ming‐Lei Guo Eugene E Fibuch Xian‐Yu Liu Eun Sang Choe Shilpa Buch Li‐Min Mao John Q Wang 《The EMBO journal》2010,29(12):2070-2081
Muscarinic acetylcholine receptors (mAChRs) are widely expressed in the mammalian brain and are essential for neuronal functions. These receptors are believed to be actively regulated by intracellular signals, although the underlying mechanisms are largely unknown. In this study, we show that Ca2+/calmodulin‐dependent protein kinase II (CaMKII) binds directly and selectively to one of five mAChR subtypes, M4 receptors (M4Rs), at their C‐terminal regions of second intracellular loops. This binding relies on Ca2+ activation of the kinase and leads to the phosphorylation of M4Rs at a specific threonine site (Thr145). Complementary in vivo studies in rat striatal neurons enriched with M4Rs confirm that rising Ca2+ recruits CaMKIIα to M4Rs to potentiate receptor signalling, which controls behavioural sensitivity to dopamine stimulation in an activity‐dependent manner. Our data identify a new model of protein–protein interactions. In a Ca2+‐sensitive manner, CaMKIIα regulates M4R efficacy and controls the acetylcholine–dopamine balance in the basal ganglia and also the dynamics of movement. 相似文献
82.
T-DNA-tagged rice plants were screened under cold- or salt-stress conditions to determine the genes involved in the molecular
mechanism for their abiotic-stress response. Line 0-165-65 was identified as a salt-responsive line. The gene responsible
for this GUS-positive phenotype was revealed by inverse PCR as OsGSK1 (O
ryza
s
ativa
g
lycogen
s
ynthase
k
inase3-like gene
1), a member of the plant GSK3/SHAGGY-like protein kinase genes and an orthologue of the Arabidopsis
b
rassinosteroid
in
sensitive
2
(BIN2), AtSK21. Northern blot analysis showed that OsGSK1 was most highly detected in the developing panicles, suggesting that its expression is developmental stage specific. Knockout
(KO) mutants of OsGSK1 showed enhanced tolerance to cold, heat, salt, and drought stresses when compared with non-transgenic segregants (NT). Overexpression
of the full-length OsGSK1 led to a stunted growth phenotype similar to the one observed with the gain-of-function BIN/AtSK21 mutant. This suggests that OsGSK1 might be a functional rice orthologue that serves as a negative regulator of brassinosteroid (BR)-signaling. Therefore, we
propose that stress-responsive OsGSK1 may have physiological roles in stress signal-transduction pathways and floral developmental processes.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Serry Koh and Sang-Choon Lee are co-first authors. 相似文献
83.
Park SH Kim CM Je BI Park SH Park SJ Piao HL Xuan YH Choe MS Satoh K Kikuchi S Lee KH Cha YS Ahn BO Ji HS Yun DW Lee MC Suh SC Eun MY Han CD 《Planta》2007,227(1):1-12
OSH6 (Oryza sativa Homeobox6) is an ortholog of lg3 (Liguleless3) in maize. We generated a novel allele, termed OSH6-Ds, by inserting a defective Ds element into the third exon of OSH6, which resulted in a truncated OSH6 mRNA. The truncated mRNA was expressed ectopically in leaf tissues and encoded the N-terminal region of OSH6, which includes
the KNOX1 and partial KNOX2 subdomains. This recessive mutant showed outgrowth of bracts or produced leaves at the basal node
of the panicle. These phenotypes distinguished it from the OSH6 transgene whose ectopic expression led to a “blade to sheath transformation” phenotype at the midrib region of leaves, similar
to that seen in dominant Lg3 mutants. Expression of a similar truncated OSH6 cDNA from the 35S promoter (35S::ΔOSH6) confirmed that the ectopic expression of this product was responsible for the aberrant bract development. These data suggest
that OSH6-Ds interferes with a developmental mechanism involved in bract differentiation, especially at the basal nodes of panicles.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
84.
85.
Yeon Sook Choi Doo Young Lee Ick Young Kim Hong Jin Kim Hong Woo Park Tae Boo Choe Ik-Hwan Kim 《Biotechnology and Bioprocess Engineering》2007,12(1):60-72
The stabilization of optimum pH for cells can cause a higher erythropoietin (EPO) production rate and a good growth rate with
the prolonged culture span in recombinant Chinese hamster ovary (r-CHO) cells. Our strategy for stabilizing the optimum pH
in this study is to reduce the lactate production by adding sodium lactate to a culture medium. When 40 mM sodium lactate
was added, a specific growth rate was decreased by approximately 22% as compared with the control culture. However the culture
longevity was extended to 187 h, and more than a 2.7-fold increase in a final accumulated EPO concentration was obtained at
40 mM of sodium lactate. On the condition that caused the high production of EPO, a specific glucose consumption rate and
lactate production rate decreased by 23.3 and 52%, respectively. Activity of lactate dehydrogenase (LDH) in r-CHO cells increased
and catalyzed the oxidation of lactate to pyruvate, together with the reverse reaction, at the addition of 40 mM sodium lactate.
The addition of 40 mM sodium lactate caused the positive effects on a cell growth and an EPO production in the absence of
carbon dioxide gas as well as in the presence of carbon dioxide gas by reducing the accumulation of lactate. 相似文献
86.
Jeong LS Gunaga P Kim HO Tosh DK Lee HW Choe SA Moon HR Gao ZG Jacobson KA Chun MW 《Nucleosides, nucleotides & nucleic acids》2007,26(8-9):1011-1014
Stereoselective functionalization of the 1'-position of 4'-thionucleosides was achieved using a stereoselective S(N)2 reaction controlled by 5-membered ring coordination. 相似文献
87.
Yu‐Chiang Lai Chandana Kondapalli Ronny Lehneck James B Procter Brian D Dill Helen I Woodroof Robert Gourlay Mark Peggie Thomas J Macartney Olga Corti Jean‐Christophe Corvol David G Campbell Aymelt Itzen Matthias Trost Miratul MK Muqit 《The EMBO journal》2015,34(22):2840-2861
Mutations in the PTEN‐induced kinase 1 (PINK1) are causative of autosomal recessive Parkinson''s disease (PD). We have previously reported that PINK1 is activated by mitochondrial depolarisation and phosphorylates serine 65 (Ser65) of the ubiquitin ligase Parkin and ubiquitin to stimulate Parkin E3 ligase activity. Here, we have employed quantitative phosphoproteomics to search for novel PINK1‐dependent phosphorylation targets in HEK (human embryonic kidney) 293 cells stimulated by mitochondrial depolarisation. This led to the identification of 14,213 phosphosites from 4,499 gene products. Whilst most phosphosites were unaffected, we strikingly observed three members of a sub‐family of Rab GTPases namely Rab8A, 8B and 13 that are all phosphorylated at the highly conserved residue of serine 111 (Ser111) in response to PINK1 activation. Using phospho‐specific antibodies raised against Ser111 of each of the Rabs, we demonstrate that Rab Ser111 phosphorylation occurs specifically in response to PINK1 activation and is abolished in HeLa PINK1 knockout cells and mutant PINK1 PD patient‐derived fibroblasts stimulated by mitochondrial depolarisation. We provide evidence that Rab8A GTPase Ser111 phosphorylation is not directly regulated by PINK1 in vitro and demonstrate in cells the time course of Ser111 phosphorylation of Rab8A, 8B and 13 is markedly delayed compared to phosphorylation of Parkin at Ser65. We further show mechanistically that phosphorylation at Ser111 significantly impairs Rab8A activation by its cognate guanine nucleotide exchange factor (GEF), Rabin8 (by using the Ser111Glu phosphorylation mimic). These findings provide the first evidence that PINK1 is able to regulate the phosphorylation of Rab GTPases and indicate that monitoring phosphorylation of Rab8A/8B/13 at Ser111 may represent novel biomarkers of PINK1 activity in vivo. Our findings also suggest that disruption of Rab GTPase‐mediated signalling may represent a major mechanism in the neurodegenerative cascade of Parkinson''s disease. 相似文献
88.
Jong In Kim Jin Young Huh Jee Hyung Sohn Sung Sik Choe Yun Sok Lee Chun Yan Lim Ala Jo Seung Bum Park Weiping Han Jae Bum Kim 《Molecular and cellular biology》2015,35(10):1686-1699
In obesity, adipocyte hypertrophy and proinflammatory responses are closely associated with the development of insulin resistance in adipose tissue. However, it is largely unknown whether adipocyte hypertrophy per se might be sufficient to provoke insulin resistance in obese adipose tissue. Here, we demonstrate that lipid-overloaded hypertrophic adipocytes are insulin resistant independent of adipocyte inflammation. Treatment with saturated or monounsaturated fatty acids resulted in adipocyte hypertrophy, but proinflammatory responses were observed only in adipocytes treated with saturated fatty acids. Regardless of adipocyte inflammation, hypertrophic adipocytes with large and unilocular lipid droplets exhibited impaired insulin-dependent glucose uptake, associated with defects in GLUT4 trafficking to the plasma membrane. Moreover, Toll-like receptor 4 mutant mice (C3H/HeJ) with high-fat-diet-induced obesity were not protected against insulin resistance, although they were resistant to adipose tissue inflammation. Together, our in vitro and in vivo data suggest that adipocyte hypertrophy alone may be crucial in causing insulin resistance in obesity. 相似文献
89.
90.
Claudia M. Nicolae Erin R. Aho Katherine N. Choe Daniel Constantin He-Juan Hu Deokjae Lee Kyungjae Myung George-Lucian Moldovan 《Nucleic acids research》2015,43(6):3143-3153
Genomic instability, a major hallmark of cancer cells, is caused by incorrect or ineffective DNA repair. Many DNA repair mechanisms cooperate in cells to fight DNA damage, and are generally regulated by post-translational modification of key factors. Poly-ADP-ribosylation, catalyzed by PARP1, is a post-translational modification playing a prominent role in DNA repair, but much less is known about mono-ADP-ribosylation. Here we report that mono-ADP-ribosylation plays an important role in homologous recombination DNA repair, a mechanism essential for replication fork stability and double strand break repair. We show that the mono-ADP-ribosyltransferase PARP14 interacts with the DNA replication machinery component PCNA and promotes replication of DNA lesions and common fragile sites. PARP14 depletion results in reduced homologous recombination, persistent RAD51 foci, hypersensitivity to DNA damaging agents and accumulation of DNA strand breaks. Our work uncovered PARP14 as a novel factor required for mitigating replication stress and promoting genomic stability. 相似文献