共查询到20条相似文献,搜索用时 229 毫秒
1.
Q.-Q. Li X.-X. Cao J.-D. Xu Q. Chen W.-J. Wang F. Tang Z.-Q. Chen X.-P. Liu Z.-D. Xu 《Cellular and molecular life sciences : CMLS》2009,66(3):504-515
We previously reported that treatment with P-glycoprotein (P-gp) substrates promotes in vitro invasion in multidrug-resistant (MDR) breast cancer cells. This effect is initiated by the P-gp pump function and mediated
by interaction of P-gp with some unknown component(s). However, the underlying mechanism(s) remains poorly understood. Here
we confirm a novel physical interaction between P-gp and cellular prion protein (PrPc). Blocking P-gp activity or depletion of PrPc inhibited paclitaxel (P-gp substrate)- induced invasion. Paclitaxel further facilitated the formation of P-gp/PrPc clusters residing in caveolar domains and promoted the association of P-gp with caveolin-1. Both caveolin-1 and the integrity
of caveolae were required for the drug-induced invasion. In addition, the P-gp/PrPc complex also played an important role in anti-apoptotic activity of MCF7/Adr cells.These data provide new insights into the
mode by which MDR breast cancers evade cytotoxic attacks from P-gp substrates and also suggest a role for P-gp/ PrPc interaction in this process.
Received 4 September 2008; received after revision 16 November 2008; accepted 18 November 2008 相似文献
2.
Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases associated with progressive oligo- and multimerization
of the prion protein (PrPC), its conformational conversion, aggregation and precipitation. We recently proposed that PrPC serves as a cell surface scaffold protein for a variety of signaling modules, the effects of which translate into wide-range
functional consequences. Here we review evidence for allosteric functions of PrPC, which constitute a common property of scaffold proteins. The available data suggest that allosteric effects among PrPC and its partners are involved in the assembly of multi-component signaling modules at the cell surface, impose upon both
physiological and pathological conformational responses of PrPC, and that allosteric dysfunction of PrPC has the potential to entail progressive signal corruption. These properties may be germane both to physiological roles of
PrPC, as well as to the pathogenesis of the TSEs and other degenerative/non-communicable diseases. 相似文献
3.
Sabine Gilch Christian Bach Gloria Lutzny Ina Vorberg Hermann M. Schätzl 《Cellular and molecular life sciences : CMLS》2009,66(24):3979-3991
The infectious agent in prion diseases consists of an aberrantly folded isoform of the cellular prion protein (PrPc), termed PrPSc, which accumulates in brains of affected individuals. Studies on prion-infected cultured cells indicate that cellular cholesterol
homeostasis influences PrPSc propagation. Here, we demonstrate that the cellular PrPSc content decreases upon accumulation of cholesterol in late endosomes, as induced by NPC-1 knock-down or treatment with U18666A.
PrPc trafficking, lipid raft association, and membrane turnover are not significantly altered by such treatments. Cellular PrPSc formation is not impaired, suggesting that PrPSc degradation is increased by intracellular cholesterol accumulation. Interestingly, PrPSc propagation in U18666A-treated cells was partially restored by overexpression of rab 9, which causes redistribution of cholesterol
and possibly of PrPSc to the trans-Golgi network. Surprisingly, rab 9 overexpression itself reduced cellular PrPSc content, indicating that PrPSc production is highly sensitive to alterations in dynamics of vesicle trafficking. 相似文献
4.
Reuter A Binkle U Stuermer CA Plattner H 《Cellular and molecular life sciences : CMLS》2004,61(16):2092-2099
A new model of caveolin association with lipid body cores has recently been proposed which may be relevant to a number of cellular processes, e.g. lipid body generation. Here we show that PrPc and reggie-1 and reggie-2 also occur in the cores of Nile Red/Bodipy-stained (neutral lipid-containing) vesicular structures and, in immunoblots, in the lipid-enriched fraction after density gradient centrifugation. These lipid-rich vesicles increase in number following cell feeding with oleic acid, differ from early endosome antigen 1- and Lamp-2-positive endosomes/lysosomes, exhibit an opaque content and lack surrounding actin staining. Our results suggest that the content of these vesicles, together with reggie-1 and -2 and PrPc, is expelled.Received 3 May 2004; received after revision 14 June 2004; accepted 23 June 2004 相似文献
5.
Glaucia N. M. Hajj Camila P. Arantes Marcos Vinicios Salles Dias Martín Roffé Bruno Costa-Silva Marilene H. Lopes Isabel Porto-Carreiro Tatiana Rabachini Flávia R. Lima Flávio H. Beraldo Marco M. A. Prado Rafael Linden Vilma R. Martins 《Cellular and molecular life sciences : CMLS》2013,70(17):3211-3227
The co-chaperone stress-inducible protein 1 (STI1) is released by astrocytes, and has important neurotrophic properties upon binding to prion protein (PrPC). However, STI1 lacks a signal peptide and pharmacological approaches pointed that it does not follow a classical secretion mechanism. Ultracentrifugation, size exclusion chromatography, electron microscopy, vesicle labeling, and particle tracking analysis were used to identify three major types of extracellular vesicles (EVs) released from astrocytes with sizes ranging from 20–50, 100–200, and 300–400 nm. These EVs carry STI1 and present many exosomal markers, even though only a subpopulation had the typical exosomal morphology. The only protein, from those evaluated here, present exclusively in vesicles that have exosomal morphology was PrPC. STI1 partially co-localized with Rab5 and Rab7 in endosomal compartments, and a dominant-negative for vacuolar protein sorting 4A (VPS4A), required for formation of multivesicular bodies (MVBs), impaired EV and STI1 release. Flow cytometry and PK digestion demonstrated that STI1 localized to the outer leaflet of EVs, and its association with EVs greatly increased STI1 activity upon PrPC-dependent neuronal signaling. These results indicate that astrocytes secrete a diverse population of EVs derived from MVBs that contain STI1 and suggest that the interaction between EVs and neuronal surface components enhances STI1–PrPC signaling. 相似文献
6.
D. Parolini M. Meregalli M. Belicchi P. Razini R. Lopa B. Del Carlo A. Farini S. Maciotta N. Bresolin L. Porretti M. Pellegrino Y. Torrente 《Cellular and molecular life sciences : CMLS》2009,66(4):697-710
Among the heterogeneous population of circulating hematopoietic and endothelial progenitors, we identified a subpopulation
of CD133+ cells displaying myogenic properties. Unexpectedly, we observed the expression of the B-cell marker CD20 in blood-derived
CD133+ stem cells. The CD20 antigen plays a role in the modulation of intracellular calcium homeostasis through signaling pathways
activation. Several observations suggest that an increase in intracellular calcium concentration ([Ca2+]i) could be involved in the etiology of the Duchenne muscular dystrophy (DMD). Here, we show that a CD20-related signaling
pathway able to induce an increase in [Ca2+]i is differently activated after brain derived neurotrophic factor (BDNF) stimulation of normal and dystrophic blood-derived
CD133+ stem cells, supporting the assumption of a “CD20-related calcium impairment-affecting dystrophic cells. Presented findings
represent the starting point toward the expansion of knowledge on pathways involved in the pathology of DMD and in the behavior
of dystrophic blood-derived CD133+ stem cells.
Received 15 October 2008; received after revision 27 November 2008; accepted 05 December 2008 相似文献
7.
E. Sick N. Niederhoffer K. Takeda Y. Landry J.-P. Gies 《Cellular and molecular life sciences : CMLS》2009,66(7):1271-1282
Mast cells play pivotal roles in allergic and inflammatory processes via distinct activation pathways. Mucosal and serosal mast cells are activated by the IgE/FcɛRI pathway, while only serosal mast
cells are activated by basic secretagogues. We show that CD47 receptors are expressed on rat peritoneal mast cells. 4N1K,
a peptide agonist of CD47, rapidly caused exocytosis. Such exocytosis required increased intracellular calcium and was inhibited
by pertussis toxin and an antibody against the βγ dimer of a Gi protein. Cooperation with integrins and glycosylphosphatidylinositol-anchored proteins was necessary, since anti-integrin
antibodies and pretreatment with phosphatidylinositol-phospholipase C reduced exocytosis. Depletion of membrane cholesterol
inhibited exocytosis and decreased CD47 in lipid rafts, consistent with a CD47/integrin/Gi protein complex being located in rafts. An anti-CD47 antibody inhibited exocytosis induced by 4N1K and by mastoparan and
spermine, suggesting that basic secretagogues might target CD47. We propose that 4N1K-stimulated mast cell exocytosis involves
a CD47/integrin/Gi protein complex.
Received 8 December 2008; received after revision 12 January 2009; accepted 29 January 2009 相似文献
8.
Didier Vilette Josquin Courte Jean Michel Peyrin Laurent Coudert Laurent Schaeffer Olivier Andréoletti Pascal Leblanc 《Cellular and molecular life sciences : CMLS》2018,75(14):2557-2574
Prions are infectious agents that cause fatal neurodegenerative diseases. Current evidence indicates that they are essentially composed of an abnormally folded protein (PrPSc). These abnormal aggregated PrPSc species multiply in infected cells by recruiting and converting the host PrPC protein into new PrPSc. How prions move from cell to cell and progressively spread across the infected tissue is of crucial importance and may provide experimental opportunity to delay the progression of the disease. In infected cells, different mechanisms have been identified, including release of infectious extracellular vesicles and intercellular transfer of PrPSc-containing organelles through tunneling nanotubes. These findings should allow manipulation of the intracellular trafficking events targeting PrPSc in these particular subcellular compartments to experimentally address the relative contribution of these mechanisms to in vivo prion pathogenesis. In addition, such information may prompt further experimental strategies to decipher the causal roles of protein misfolding and aggregation in other human neurodegenerative diseases. 相似文献
9.
Prion diseases are fatal neurodegenerative and infectious disorders of humans and animals, characterized by structural transition
of the host-encoded cellular prion protein (PrPc) into the aberrantly folded pathologic isoform PrPSc. RNA, DNA or peptide aptamers are classes of molecules which can be selected from complex combinatorial libraries for high
affinity and specific binding to prion proteins and which might therefore be useful in diagnosis and therapy of prion diseases.
Nucleic acid aptamers, which can be chemically synthesized, stabilized and immobilized, appear more suitable for diagnostic
purposes, allowing use of PrPSc as selection target. Peptide aptamers facilitate appropriate intracellular expression, targeting and re-routing without losing
their binding properties to PrP, a requirement for potential therapeutic gene transfer experiments in vivo. Elucidation of
structural properties of peptide aptamers might be used as basis for rational drug design, providing another attractive application
of peptide aptamers in the search for effective anti-prion strategies. 相似文献
10.
Yuan J Dong Z Guo JP McGeehan J Xiao X Wang J Cali I McGeer PL Cashman NR Bessen R Surewicz WK Kneale G Petersen RB Gambetti P Zou WQ 《Cellular and molecular life sciences : CMLS》2008,65(4):631-643
Human prion diseases are characterized by the accumulation in the brain of proteinase K (PK)-resistant prion protein designated
PrP27 – 30 detectable by the 3F4 antibody against human PrP109 – 112. We recently identified a new PK-resistant PrP species,
designated PrP*20, in uninfected human and animal brains. It was preferentially detected with the 1E4 antibody against human PrP 97 – 108 but
not with the anti-PrP 3F4 antibody, although the 3F4 epitope is adjacent to the 1E4 epitope in the PrP*20 molecule. The present study reveals that removal of the N-terminal amino acids up to residue 91 significantly increases accessibility
of the 1E4 antibody to PrP of brains and cultured cells. In contrast to cells expressing wild-type PrP, cells expressing pathogenic
mutant PrP accumulate not only PrP*20 but also a small amount of 3F4-detected PK-resistant PrP27 – 30. Remarkably, during the course of human prion disease, a
transition from an increase in 1E4-detected PrP*20 to the occurrence of the 3F4-detected PrP27 – 30 was observed. Our study suggests that an increase in the level of PrP*20 characterizes the early stages of prion diseases.
Received 17 October 2007; received after revision 5 December 2007; accepted 14 December 2007 相似文献
11.
Linda Reinhard Henning Tidow Michael J. Clausen Poul Nissen 《Cellular and molecular life sciences : CMLS》2013,70(2):205-222
The Na+,K+-ATPase, or sodium pump, is well known for its role in ion transport across the plasma membrane of animal cells. It carries out the transport of Na+ ions out of the cell and of K+ ions into the cell and thus maintains electrolyte and fluid balance. In addition to the fundamental ion-pumping function of the Na+,K+-ATPase, recent work has suggested additional roles for Na+,K+-ATPase in signal transduction and biomembrane structure. Several signaling pathways have been found to involve Na+,K+-ATPase, which serves as a docking station for a fast-growing number of protein interaction partners. In this review, we focus on Na+,K+-ATPase as a signal transducer, but also briefly discuss other Na+,K+-ATPase protein–protein interactions, providing a comprehensive overview of the diverse signaling functions ascribed to this well-known enzyme. 相似文献
12.
Mornon JP Prat K Dupuis F Boisset N Callebaut I 《Cellular and molecular life sciences : CMLS》2002,59(12):2144-2154
Prion diseases are neurodegenerative disorders associated with a conformational conversion of the prion PrP protein, in which
the β-strand content increases and that of the α helix decreases. However, the structure of the pathogenous form PrPSc, occurring after conformational conversion of the normal cellular form PrPC, is not yet known. From sequence analysis, we have previously proposed that helix H2 of the prion PrPC structure might be a key region for this structural conversion. More recently, we identified the TATA box-binding protein
fold as a putative scaffold that may locally satisfy the predicted secondary-structure organisation of PrPSc. In the present analysis, we detail the schematic construction of PrPSc monomeric and dimeric models, based on this hypothesis. These models are globally compatible with available data and therefore
may provide further insights into the structurally and functionally elusive PrP protein.
Some comments are also devoted to a comparison of the yeast Ure2p prion and animal prions.
Received 29 July 2002; received after revision 24 October 2002; accepted 24 October 2002
RID="*"
ID="*"Corresponding author. 相似文献
13.
Role of Sam68 as an adaptor protein in signal transduction 总被引:3,自引:0,他引:3
Najib S Martín-Romero C González-Yanes C Sánchez-Margalet V 《Cellular and molecular life sciences : CMLS》2005,62(1):36-43
Sam68, the substrate of Src in mitosis, belongs to the family of RNA binding proteins. Sam68 contains consensus sequences to interact with other proteins via specific domains. Thus, Sam68 has various proline-rich sequences to interact with SH3 domain-containing proteins. Moreover, Sam68 also has a C-terminal domain rich in tyrosine residues that is a substrate for tyrosine kinases. Tyrosine phosphorylation of Sam68 promotes its interaction with SH2 containing proteins. The association of Sam68 with SH3 domain-containing proteins, and its tyrosine phosphorylation may negatively regulate its RNA binding activity. The presence of these consensus sequences to interact with different domains allows this protein to participate in signal transduction pathways triggered by tyrosine kinases. Thus, Sam68 participates in the signaling of T cell receptors, leptin and insulin receptors. In these systems Sam68 is tyrosine phosphorylated and recruited to specific signaling complexes. The participation of Sam68 in signaling suggests that it may function as an adaptor molecule, working as a dock to recruit other signaling molecules. Finally, the connection between this role of Sam68 in protein-protein interaction with RNA binding activity may connect signal transduction of tyrosine kinases with the regulation of RNA metabolism.Received 16 July 2004; received after revision 12 August 2004; accepted 18 August 2004 相似文献
14.
Fu WX Gong SY Qian XP Li Y Zhu ML Dong XY Li Y Chen WF 《Cellular and molecular life sciences : CMLS》2004,61(15):1935-1945
Mouse platelet basic protein (CXCL7/mPBP) was cloned from thymic stromal cells and further identification
indicated that it was expressed in thymic monocytes/macrophages (Mo/Ms). Recombinant mPBP was
chemoattractive for target cells of polymorphonuclear leucocytes, peritoneal Mo/Ms and splenic lymphocytes
with distinct potencies. CXCR2 was identified to be a cognate receptor for mPBP. Mouse thymocyte subsets of
CD4-CD8- double-negative (DN),
CD4+CD8+ double-positive (DP),
CD4+CD8- single-positive (CD4SP)
and CD4-CD8+ single-positive (CD8SP) expressed cell surface
CXCR2 with different positive percentages and expression levels. mPBP was chemoattractive for thymocyte subsets
with the potency order DN>DP> CD8SP>CD4SP, consistent with the levels of CXCR2 expressed on the
respective cells. Thus, mPBP in thymus is functionally redundant with chemokine CXCL12/ SDF-1. Moreover, our
finding that thymic Mo/Ms can produce mPBP implies that they may have other functions apart from acting as
scavengers in thymus.Received 25 March 2004; received after revision 10 May 2004; accepted 8 June 2004 相似文献
15.
Catherine Aude-Garcia Christian Villiers Serge M. Candéias Catherine Garrel Caroline Bertrand Véronique Collin Patrice N. Marche Evelyne Jouvin-Marche 《Cellular and molecular life sciences : CMLS》2011,68(4):687-696
The cellular prion glycoprotein (PrPC) is ubiquitously expressed but its physiologic functions remain enigmatic, particularly in the immune system. Here, we demonstrate
in vitro and in vivo that PrPC is involved in T lymphocytes response to oxidative stress. By monitoring the intracellular level of reduced glutathione,
we show that PrP−/− thymocytes display a higher susceptibility to H2O2 exposure than PrP+/+ cells. Furthermore, we find that in mice fed with a restricted diet, a regimen known to increase the intracellular level
of ROS, PrP−/− thymocytes are more sensitive to oxidative stress. PrPC function appears to be specific for oxidative stress, since no significant differences are observed between PrP−/− and PrP+/+ mice exposed to other kinds of stress. We also show a marked evolution of the redox status of T cells throughout differentiation
in the thymus. Taken together, our results clearly ascribe to PrPC a protective function in thymocytes against oxidative stress. 相似文献
16.
Shabaana AK Kulangara K Semac I Parel Y Ilangumaran S Dharmalingam K Chizzolini C Hoessli DC 《Cellular and molecular life sciences : CMLS》2005,62(2):179-187
Lipoarabinomannans (LAMs) are major lipoglycans of the mycobacterial envelope and constitute immunodominant epitopes of mycobacteria. In this paper, we show that mannose-capped (ManLAM) and non-mannose- capped (PILAM) mycobacterial lipoglycans insert into T helper cell rafts without apparent binding to known receptors. T helper cells modified by the insertion of PILAM responded to CD3 cross-linking by decreasing type 1 (IL-2 and IFN-) and increasing type 2 (IL-4 and IL-5) cytokine production. Modification by the mannose-capped ManLAMs had similar, but more limited effects on T helper cell cytokine production. When incorporated into isolated rafts, PILAMs modulated membrane-associated kinases in a dose-dependent manner, inducing increased phosphorylation of Src kinases and Cbp/PAG in Th1 rafts, while decreasing phosphorylation of the same proteins in Th2 rafts. Mycobacterial lipoglycans thus modify the signalling machineries of rafts/microdomains in T helper cells, a modification of the membrane organization that eventually leads to an overall enhancement of type 2 and inhibition of type 1 cytokine production.Received 9 September 2004; received after revision 14 October 2004; accepted 11 November 2004A. K. Shabaana and K. Kulangara made equal contributions to this work. 相似文献
17.
Xingjian Jin Ashraf M. Mohieldin Brian S. Muntean Jill A. Green Jagesh V. Shah Kirk Mykytyn Surya M. Nauli 《Cellular and molecular life sciences : CMLS》2014,71(11):2165-2178
Primary cilia with a diameter of ~200 nm have been implicated in development and disease. Calcium signaling within a primary cilium has never been directly visualized and has therefore remained a speculation. Fluid-shear stress and dopamine receptor type-5 (DR5) agonist are among the few stimuli that require cilia for intracellular calcium signal transduction. However, it is not known if these stimuli initiate calcium signaling within the cilium or if the calcium signal originates in the cytoplasm. Using an integrated single-cell imaging technique, we demonstrate for the first time that calcium signaling triggered by fluid-shear stress initiates in the primary cilium and can be distinguished from the subsequent cytosolic calcium response through the ryanodine receptor. Importantly, this flow-induced calcium signaling depends on the ciliary polycystin-2 calcium channel. While DR5-specific agonist induces calcium signaling mainly in the cilioplasm via ciliary CaV1.2, thrombin specifically induces cytosolic calcium signaling through the IP3 receptor. Furthermore, a non-specific calcium ionophore triggers both ciliary and cytosolic calcium responses. We suggest that cilia not only act as sensory organelles but also function as calcium signaling compartments. Cilium-dependent signaling can spread to the cytoplasm or be contained within the cilioplasm. Our study thus provides the first model to understand signaling within the cilioplasm of a living cell. 相似文献
18.
Functions and pathologies of BiP and its interaction partners 总被引:1,自引:1,他引:0
J. Dudek J. Benedix S. Cappel M. Greiner C. Jalal L. Müller R. Zimmermann 《Cellular and molecular life sciences : CMLS》2009,66(9):1556-1569
The endoplasmic reticulum (ER) is involved in a variety of essential and interconnected processes in human cells, including
protein biogenesis, signal transduction, and calcium homeostasis. The central player in all these processes is the ER-lumenal
polypeptide chain binding protein BiP that acts as a molecular chaperone. BiP belongs to the heat shock protein 70 (Hsp70)
family and crucially depends on a number of interaction partners, including co-chaperones, nucleotide exchange factors, and
signaling molecules. In the course of the last five years, several diseases have been linked to BiP and its interaction partners,
such as a group of infectious diseases that are caused by Shigella toxin producing E. coli. Furthermore, the inherited diseases Marinesco-Sj?gren syndrome, autosomal dominant polycystic liver disease, Wolcott-Rallison
syndrome, and several cancer types can be considered BiP-related diseases. This review summarizes the physiological and pathophysiological
characteristics of BiP and its interaction partners.
Received 20 November 2008; received after revision 09 December 2008; accepted 12 December 2008 相似文献
19.
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
20.
Calcium signaling in plants 总被引:9,自引:0,他引:9
Changes in the cytosolic concentration of calcium ions ([Ca2+]i) play a key second messenger role in signal transduction. These changes are visualized by making use of either Ca2+-sensitive fluorescent dyes or the Ca2+-sensitive photoprotein, aequorin. Here we describe the advances made over the last 10 years or so, which have conclusively
demonstrated a second messenger role for [Ca2+]i in a few model plant systems. Characteristic changes in [Ca2+]i have been seen to precede the responses of plant cells and whole plants to physiological stimuli. This has had a major impact
on our understanding of cell signaling in plants. The next challenge will be to establish how the Ca2+ signals are encrypted and decoded in order to provide specificity, and we discuss the current understanding of how this may
be achieved. 相似文献