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511.
Se Hwan Mun Na Young Ko Hyuk Soon Kim Jie Wan Kim Do Kyun Kim A-Ram Kim Seung Hyun Lee Yong-Gil Kim Chang Keun Lee Seoung Hoon Lee Bo Kyung Kim Michael A. Beaven Young Mi Kim Wahn Soo Choi 《Cellular and molecular life sciences : CMLS》2010,67(22):3883-3892
Interleukin (IL)-33 is a recently described pro-inflammatory cytokine. Here we demonstrate IL-33 as a regulator of functional osteoclasts (OCs) from human CD14+ monocytes. IL-33 stimulates formation of tartrate-resistant acid phosphatase (TRAP)+ multinuclear OCs from monocytes. This action was suppressed by anti-ST2 antibody, suggesting that IL-33 acts through its receptor ST2, but not by the receptor activator of NF-κB ligand (RANKL) decoy, osteoprotegerin, or anti-RANKL antibody. IL-33 stimulated activating phosphorylations of signaling molecules in monocytes that are critical for OC development. These included Syk, phospholipase Cγ2, Gab2, MAP kinases, TAK-1, and NF-κB. IL-33 also enhanced expression of OC differentiation factors including TNF-α receptor-associated factor 6 (TRAF6), nuclear factor of activated T cells cytoplasmic 1, c-Fos, c-Src, cathepsin K, and calcitonin receptor. IL-33 eventually induced bone resorption. This study suggests that the osteoclastogenic property of IL-33 is mediated through TRAF6 as well as the immunoreceptor tyrosine-based activation motif-dependent Syk/PLCγ pathway in human CD14+ monocytes. 相似文献
512.
Julie Patenaude Michele D’Elia Claudine Hamelin Jacques Bernier 《Cellular and molecular life sciences : CMLS》2010,67(8):1315-1329
Burn injury causes an immunosuppression associated with suppressed adaptive immune function. Dendritic cells (DCs) are APCs
for which signaling via their Toll-like receptors (TLRs) induces their maturation and activation, which is essential for the
adaptive immune response. In this study, we examined if burn injury alters the TLR activity of splenic DCs. After injury,
we noticed that DC functions were impaired, characterized by a suppressed capacity to prime naive T cells when triggering
the TLR4 signaling cascade using specific ligands (LPS or rHSP60). The observed perturbations on LPS-primed DCs isolated from
burned mice exhibited significantly diminished IL-12p40 production and enhanced IL-10 secretion-associated impairment in mitogen-activated
protein kinase activation. Interestingly, we observed a decrease of TLR4/MD-2 expression on the CD8α+ DC subset that persisted following LPS stimulation. The altered TLR4 expression on LPS-stimulated CD8α+ DCs was associated with reduced capacity to produce IL-12 after stimulation. Our results suggested that TLR4 reactivity on
DCs, especially CD8α+ DCs, is disturbed after burn injury. 相似文献
513.
Potassium and sodium transport in non-animal cells: the Trk/Ktr/HKT transporter family 总被引:1,自引:1,他引:0
C. Corratgé-Faillie M. Jabnoune S. Zimmermann A.-A. Véry C. Fizames H. Sentenac 《Cellular and molecular life sciences : CMLS》2010,67(15):2511-2532
Bacterial Trk and Ktr, fungal Trk and plant HKT form a family of membrane transporters permeable to K+ and/or Na+ and characterized by a common structure probably derived from an ancestral K+ channel subunit. This transporter family, specific of non-animal cells, displays a large diversity in terms of ionic permeability,
affinity and energetic coupling (H+–K+ or Na+–K+ symport, K+ or Na+ uniport), which might reflect a high need for adaptation in organisms living in fluctuating or dilute environments. Trk/Ktr/HKT
transporters are involved in diverse functions, from K+ or Na+ uptake to membrane potential control, adaptation to osmotic or salt stress, or Na+ recirculation from shoots to roots in plants. Structural analyses of bacterial Ktr point to multimeric structures physically
interacting with regulatory subunits. Elucidation of Trk/Ktr/HKT protein structures along with characterization of mutated
transporters could highlight functional and evolutionary relationships between ion channels and transporters displaying channel-like
features. 相似文献
514.
Voltage-gated calcium channels are important mediators of calcium influx into electrically excitable cells. The amount of
calcium entering through this family of channel proteins is not only determined by the functional properties of channels embedded
in the plasma membrane but also by the numbers of channels that are expressed at the cell surface. The trafficking of channels
is controlled by numerous processes, including co-assembly with ancillary calcium channel subunits, ubiquitin ligases, and
interactions with other membrane proteins such as G protein coupled receptors. Here we provide an overview about the current
state of knowledge of calcium channel trafficking to the cell membrane, and of the mechanisms regulating the stability and
internalization of this important ion channel family. 相似文献
515.
Machnicka B Grochowalska R Bogusławska DM Sikorski AF Lecomte MC 《Cellular and molecular life sciences : CMLS》2012,69(2):191-201
This review focuses on the recent advances in functions of spectrins in non-erythroid cells. We discuss new data concerning
the commonly known role of the spectrin-based skeleton in control of membrane organization, stability and shape, and tethering
protein mosaics to the cellular motors and to all major filament systems. Particular effort has been undertaken to highlight
recent advances linking spectrin to cell signaling phenomena and its participation in signal transduction pathways in many
cell types. 相似文献
516.
517.
Farooqui AA Farooqui T Panza F Frisardi V 《Cellular and molecular life sciences : CMLS》2012,69(5):741-762
The metabolic syndrome is a cluster of common pathologies: abdominal obesity linked to an excess of visceral fat, insulin
resistance, dyslipidemia and hypertension. At the molecular level, metabolic syndrome is accompanied not only by dysregulation
in the expression of adipokines (cytokines and chemokines), but also by alterations in levels of leptin, a peptide hormone
released by white adipose tissue. These changes modulate immune response and inflammation that lead to alterations in the
hypothalamic ‘bodyweight/appetite/satiety set point,’ resulting in the initiation and development of metabolic syndrome. Metabolic
syndrome is a risk factor for neurological disorders such as stroke, depression and Alzheimer’s disease. The molecular mechanism
underlying the mirror relationship between metabolic syndrome and neurological disorders is not fully understood. However,
it is becoming increasingly evident that all cellular and biochemical alterations observed in metabolic syndrome like impairment
of endothelial cell function, abnormality in essential fatty acid metabolism and alterations in lipid mediators along with
abnormal insulin/leptin signaling may represent a pathological bridge between metabolic syndrome and neurological disorders
such as stroke, Alzheimer’s disease and depression. The purpose of this review is not only to describe the involvement of
brain in the pathogenesis of metabolic syndrome, but also to link the pathogenesis of metabolic syndrome with neurochemical
changes in stroke, Alzheimer’s disease and depression to a wider audience of neuroscientists with the hope that this discussion
will initiate more studies on the relationship between metabolic syndrome and neurological disorders. 相似文献
518.
KI Cho K Searle M Webb H Yi PA Ferreira 《Cellular and molecular life sciences : CMLS》2012,69(20):3511-3527
Many components and pathways transducing multifaceted and deleterious effects of stress stimuli remain ill-defined. The Ran-binding protein 2 (RanBP2) interactome modulates the expression of a range of clinical and cell-context-dependent manifestations upon a variety of stressors. We examined the role of Ranbp2 haploinsufficiency on cellular and metabolic manifestations linked to tyrosine-hydroxylase (TH(+)) dopaminergic neurons and glial cells of the brain and retina upon acute challenge to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a parkinsonian neurotoxin, which models facets of Parkinson disease. MPTP led to stronger akinetic parkinsonism and slower recovery in Ranbp2 (+/-) than wild-type mice without viability changes of brain TH(+)-neurons of either genotype, with the exception of transient nuclear atypia via changes in chromatin condensation of Ranbp2 (+/-) TH(+)-neurons. Conversely, the number of wild-type retinal TH(+)-amacrine neurons compared to Ranbp2 (+/-) underwent milder declines without apoptosis followed by stronger recoveries without neurogenesis. These phenotypes were accompanied by a stronger rise of EdU(+)-proliferative cells and non-proliferative gliosis of GFAP(+)-Müller cells in wild-type than Ranbp2 (+/-) that outlasted the MPTP-insult. Finally, MPTP-treated wild-type and Ranbp2 (+/-) mice present distinct metabolic footprints in the brain or selective regions thereof, such as striatum, that are supportive of RanBP2-mediated regulation of interdependent metabolic pathways of lysine, cholesterol, free-fatty acids, or their β-oxidation. These studies demonstrate contrasting gene-environment phenodeviances and roles of Ranbp2 between dopaminergic and glial cells of the brain and retina upon oxidative stress-elicited signaling and factors triggering a continuum of metabolic and cellular manifestations and proxies linked to oxidative stress, and chorioretinal and neurological disorders such as Parkinson. 相似文献
519.
van der Meijden PE Feijge MA Swieringa F Gilio K Nergiz-Unal R Hamulyák K Heemskerk JW 《Cellular and molecular life sciences : CMLS》2012,69(20):3481-3492
The fibrin(ogen) receptor, integrin α(IIb)β(3), has a well-established role in platelet spreading, aggregation and clot retraction. How α(IIb)β(3) contributes to platelet-dependent coagulation is less well resolved. Here, we demonstrate that the potent suppressing effect of clinically used α(IIb)β(3) blockers on tissue factor-induced thrombin generation is linked to diminished platelet Ca(2+) responses and phosphatidylserine (PS) exposure. The same blockers suppress these responses in platelets stimulated with collagen and thrombin receptor agonists, whereas added fibrinogen potentiates these responses. In platelets spreading on fibrinogen, outside-in α(IIb)β(3) signaling similarly enhances thrombin-induced Ca(2+) rises and PS exposure. These responses are reduced in α(IIb)β(3)-deficient platelets from patients with Glanzmann's thrombasthenia. Furthermore, the contribution of α(IIb)β(3) to tissue factor-induced platelet Ca(2+) rises, PS exposure and thrombin generation in plasma are fully dependent on Syk kinase activity. Tyrosine phosphorylation analysis confirms a key role of Syk activation, which is largely but not exclusively dependent on α(IIb)β(3) activation. It is concluded that the majority of tissue factor-induced procoagulant activity of platelets relies on Syk activation and ensuing Ca(2+) signal generation, and furthermore that a considerable part of Syk activation relies on α(IIb)β(3) signaling. These results hence point to a novel role of Syk in integrin-dependent thrombin generation. 相似文献
520.
Lu W Schneider M Neumann S Jaeger VM Taranum S Munck M Cartwright S Richardson C Carthew J Noh K Goldberg M Noegel AA Karakesisoglou I 《Cellular and molecular life sciences : CMLS》2012,69(20):3493-3509
Nesprins-1/-2/-3/-4 are nuclear envelope proteins, which connect nuclei to the cytoskeleton. The largest nesprin-1/-2 isoforms (termed giant) tether F-actin through their N-terminal actin binding domain (ABD). Nesprin-3, however, lacks an ABD and associates instead to plectin, which binds intermediate filaments. Nesprins are integrated into the outer nuclear membrane via their C-terminal KASH-domain. Here, we show that nesprin-1/-2 ABDs physically and functionally interact with nesprin-3. Thus, both ends of nesprin-1/-2 giant are integrated at the nuclear surface: via the C-terminal KASH-domain and the N-terminal ABD-nesprin-3 association. Interestingly, nesprin-2 ABD or KASH-domain overexpression leads to increased nuclear areas. Conversely, nesprin-2 mini (contains the ABD and KASH-domain but lacks the massive nesprin-2 giant rod segment) expression yields smaller nuclei. Nuclear shrinkage is further enhanced upon nesprin-3 co-expression or microfilament depolymerization. Our findings suggest that multivariate intermolecular nesprin interactions with the cytoskeleton form a lattice-like filamentous network covering the outer nuclear membrane, which determines nuclear size. 相似文献