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1.
Claire Flaujac Siham Boukour Elisabeth Cramer-Bordé 《Cellular and molecular life sciences : CMLS》2010,67(4):545-556
Thrombocytopenia is a frequent complication of viral infections providing evidence that interaction of platelets with viruses
is an important pathophysiological phenomenon. Multiple mechanisms are involved depending on the nature of the viruses involved.
These include immunological platelet destruction, inappropriate platelet activation and consumption, and impaired megakaryopoiesis.
Viruses bind platelets through specific receptors and identified ligands, which lead to mutual alterations of both the platelet
host and the viral aggressor. We have shown that HIV-1 viruses are internalized specifically in platelets and megakaryocytes,
where they can be either sheltered, unaltered (with potential transfer of the viruses into target organs), or come in contact
with platelet secretory products leading to virus destruction and facilitated platelet clearance. In this issue, we have reviewed
the various pathways that platelets use in order to interact with viruses, HIV and others. This review also shows that more
work is still needed to precisely identify platelet roles in viral infections, and to answer the challenge of viral safety
in platelet transfusion. 相似文献
2.
Regulation of insulin receptor function 总被引:1,自引:0,他引:1
Youngren JF 《Cellular and molecular life sciences : CMLS》2007,64(7-8):873-891
Resistance to the biological actions of insulin contributes to the development of type 2 diabetes and risk of cardiovascular
disease. A reduced biological response to insulin by tissues results from an impairment in the cascade of phosphorylation
events within cells that regulate the activity of enzymes comprising the insulin signaling pathway. In most models of insulin
resistance, there is evidence that this decrement in insulin signaling begins with either the activation or substrate kinase
activity of the insulin receptor (IR), which is the only component of the pathway that is unique to insulin action. Activation
of the IR can be impaired by post-translational modifications of the protein involving serine phosphorylation, or by binding
to inhibiting proteins such as PC-1 or members of the SOCS or Grb protein families. The impact of these processes on the conformational
changes and phosphorylation events required for full signaling activity, as well as the role of these mechanisms in human
disease, is reviewed in this article.
Received 3 August 2006; received after revision 1 December 2006; accepted 8 January 2007 相似文献
3.
Talos IF Mian AZ Zou KH Hsu L Goldberg-Zimring D Haker S Bhagwat JG Mulkern RV 《Cellular and molecular life sciences : CMLS》2006,63(10):1106-1124
The introduction and development, over the last three decades, of magnetic resonance (MR) imaging and MR spectroscopy technology
for in vivo studies of the human brain represents a truly remarkable achievement, with enormous scientific and clinical ramifications.
These effectively non-invasive techniques allow for studies of the anatomy, the function and the metabolism of the living
human brain. They have allowed for new understandings of how the healthy brain works and have provided insights into the mechanisms
underlying multiple disease processes which affect the brain. Different MR techniques have been developed for studying anatomy,
function and metabolism. The primary focus of this review is to describe these different methodologies and to briefly review
how they are being employed to more fully appreciate the intricacies associated with the organ, which most distinctly differentiates
the human species from the other animal forms on earth.
Received 1 November 2005; received after revision 11 January 2006; accepted 25 January 2006 相似文献
4.
Arterial thrombosis is the single most common cause of death and disability in industrialized societies and is the primary
pathogenic mechanism underlying acute myocardial infarction and ischemic stroke. Platelets play a central role in this process,
and as a consequence, a great deal of effort has gone into identifying the mechanisms regulating the adhesive function of
platelets. Platelet adhesion is controlled by intracellular signaling pathways, with growing evidence for a major role for
phosphoinositide 3-kinases (PI3Ks) in this process. Platelets express all type I PI3K isoforms, including p110α, p110β, p110δ
and p110γ, with recent evidence suggesting important roles for p110γ and p110β in regulating distinct phases of the platelet
activation process. Deficiency of p110 γ or inhibition of p110β produces a marked defect in arterial thrombosis without a
corresponding increase in bleeding time, raising the possibility that inhibition of one or more PI3K isoforms may represent
an effective antithrombotic approach.
Received 3 January 2006; received after revision 20 February 2006; accepted 20 February 2006 相似文献
5.
Lysophospholipids have long been recognized as membrane phospholipid metabolites, but only recently has their role as intercellular
signaling molecules been appreciated. Two of the best-studied lysophospholipids, LPA and S1P, signal through cognate G-protein-coupled
receptors to activate many well-known intracellular signaling pathways, leading to a variety of biologically important cell
responses. Lysophospholipids and their receptors have been found in a wide range of tissues and cell types, indicating their
importance in many physiological processes, including reproduction, vascular development, cancer and nervous system function.
This article will focus on the most recent findings regarding the biological functions of lysophospholipids in mammalian systems,
specifically as they relate to health and disease.
Received 5 April 2006; received after revision 22 June 2006; accepted 9 August 2006 相似文献
6.
Bosch-Comas A Lindsten K Gonzàlez-Duarte R Masucci MG Marfany G 《Cellular and molecular life sciences : CMLS》2006,63(6):723-734
The biological functions of the more than one hundred genes coding for deubiquitinating enzymes in the human genome remain
mostly unknown. The USP25 gene, located at 21q11.2, encodes three protein isoforms produced by alternative splicing. While
two of the isoforms are expressed nearly ubiquituously, the expression of the longer USP25 isoform (USP25m) is restricted
to muscular tissues and is upregulated during myogenesis. USP25m interacts with three sarcomeric proteins: actin alpha-1 (ACTA1),
filamin C (FLNC), and myosin binding protein C1 (MyBPC1), which are critically involved in muscle differentiation and maintenance,
and have been implicated in the pathogenesis of severe myopathies. Biochemical analyses demonstrated that MyBPC1 is a short-lived
proteasomal substrate, and its degradation is prevented by over-expression of USP25m but not by other USP25 isoforms. In contrast,
ACTA1 and FLNC appear to be stable proteins, indicating that their interaction with USP25m is not related to their turnover
rate.
Received 7 November 2005; received after revision 7 January 2006; accepted 13 January 2006 相似文献
7.
Edouard T Montagner A Dance M Conte F Yart A Parfait B Tauber M Salles JP Raynal P 《Cellular and molecular life sciences : CMLS》2007,64(13):1585-1590
Activating and inactivating mutations of SHP-2 are responsible, respectively, for the Noonan (NS) and the LEOPARD (LS) syndromes.
Clinically, these developmental disorders overlap greatly, resulting in the apparent paradox of similar diseases caused by
mutations that oppositely influence SHP-2 phosphatase activity. While the mechanisms remain unclear, recent functional analysis
of SHP-2, along with the identification of other genes involved in NS and in other related syndromes (neurofibromatosis-1,
Costello and cardio-facio-cutaneous syndromes), strongly suggest that Ras/MAPK represents the major signaling pathway deregulated
by SHP-2 mutants. We discuss the idea that, with the exception of LS mutations that have been shown to exert a dominant negative
effect, all disease-causing mutations involved in Ras/MAPK-mediated signaling, including SHP-2, might lead to enhanced MAPK
activation. This suggests that a narrow range of MAPK signaling is required for appropriate development. We also discuss the
possibility that LS mutations may not simply exhibit dominant negative activity.
Received 30 November 2006; received after revision 8 February 2007; accepted 13 March 2007 相似文献
8.
9.
Hearing molecules: contributions from genetic deafness 总被引:1,自引:0,他引:1
Considerable progress has been made over the past decade identifying many genes associated with deafness. With the identification
of these hereditary deafness genes and the proteins they encode, molecular elements of basic hearing mechanisms emerge. As
functional studies of these molecular elements become available, we can put together the pieces of the puzzle and begin to
reach an understanding of the molecular mechanisms of hearing. The goal of this review is to discuss studies over the past
decade that address the function of the proteins implicated in genetic deafness and to place them in the context of basic
molecular mechanisms in hearing. The first part of this review highlights structural and functional features of the cochlea
and auditory nerve. This background will provide a context for the second part, which addresses the molecular mechanisms underlying
cochlear function as elucidated by genetic causes of deafness.
Received 20 September 2006; received after revision 24 October 2006; accepted 5 December 2006 相似文献
10.
Calorie restriction and the nutrient sensing signaling pathways 总被引:3,自引:0,他引:3
Calorie restriction (CR) is the most potent regimen known to extend the life span in multiple species. CR has also been shown
to ameliorate several age-associated disorders in mammals and perhaps humans. CR induces diverse metabolic changes in organisms,
and it is currently unclear whether and how these metabolic changes lead to life span extension. Recent studies in model systems
have provided insight into the molecular mechanisms by which CR extends life span. In this review, we summarize and provide
recent updates on multiple nutrient signaling pathways that have been connected to CR and longevity regulation. The roles
of highly conserved longevity regulators – the Sirtuin family – in CR are also discussed.
Received 25 August 2006; received after revision 9 October 2006; accepted 13 December 2006 相似文献
11.
C. Akgul 《Cellular and molecular life sciences : CMLS》2009,66(8):1326-1336
Resistance to apoptosis is a common challenge in human malignancies contributing to both progress of cancer and resistance
to conventional therapeutics. Abnormalities in a variety of cell intrinsic and extrinsic molecular mechanisms cooperatively
promote tumor formation. Therapeutic approaches that specifically target components of these molecular mechanisms are getting
widespread attention. Mcl-1 is a highly expressed pro-survival protein in human malignancies and its cellular expression is
tightly regulated via multiple mechanisms. Mcl-1 differs from other members of the Bcl-2 family in having a very short half-life. So inhibition
of its expression and/or neutralization of its anti-apoptotic function will rapidly make Mcl-1-dependent cells more susceptible
to apoptosis and provide an opportunity to combat several types of cancers. This review summarizes the current knowledge on
the regulation of Mcl-1 expression and discusses the alternative approaches targeting Mcl-1 in human cancer cells whose survivals
mainly depend on Mcl-1.
Received 6 October 2008; received after revision 21 October 2008; accepted 10 November 2008 相似文献
12.
The function of apolipoproteins L 总被引:1,自引:0,他引:1
The function of the proteins of the apolipoprotein L (apoL) family is largely unknown. These proteins are classically thought
to be involved in lipid transport and metabolism, mainly due to the initial discovery that a secreted member of the family,
apoL-I, is associated with high-density lipoprotein particles. However, the other members of the family are believed to be
intracellular. The recent unravelling of the mechanism by which apoL-I kills African trypanosomes, as well as the increasing
evidence for modulation of apoL expression in various pathological processes, provides new insights about the functions of
these proteins. ApoLs share structural and functional similarities with proteins of the Bcl-2 family. Based on the activity
of apoL-I in trypanosomes and the comparison with Bcl-2 proteins, we propose that apoLs could function as ion channels of
intracellular membranes and be involved in mechanisms triggering programmed cell death.
Received 28 February 2006; received after revision 18 May 2006; accepted 2 June 2006 相似文献
13.
Joshi S Guleria RS Pan J Bayless KJ Davis GE Dipette D Singh US 《Cellular and molecular life sciences : CMLS》2006,63(23):2859-2870
Developmental exposure to ethanol impairs fetal brain development and causes fetal alcohol syndrome. Although the cerebellum
is one of the most alcohol-sensitive brain areas, signaling mechanisms underlying the deleterious effects of ethanol on developing
cerebellar granule neurons (CGNs) are largely unknown. Here we describe the effects of in vivo ethanol exposure on neurite formation in CGNs and on the activation of Rho GTPases (RhoA and Rac1), regulators of neurite
formation. Exposure of 7-day-old rat pups to ethanol for 3 h moderately increased blood alcohol concentration (BAC) (∼40 mM)
and inhibited neurite formation and Rac1 activation in CGNs. Longer exposure to ethanol for 5 h resulted in higher BAC (∼80 mM),
induced apoptosis, inhibited Rac1, and activated RhoA. Studies demonstrated a regulatory role of Rho GTPases in differentiation
of cerebellar neurons, and indicated that ethanol-associated impairment of Rho GTPase signaling might contribute to brain
defects observed in fetal alcohol syndrome.
Received 16 July 2006; received after revision 12 September 2006; accepted 13 October 2006 相似文献
14.
The semaphorin proteins were identified originally as axonal guidance factors functioning during neuronal development. In addition to this function, several semaphorins play diverse roles outside the nervous system. The class 4 semaphorin CD100/Sema4D, which utilizes plexin-B1 and CD72 as receptors, exerts important biological effects on a variety of cells, including the neuronal, epithelial and immune cells. Here, we review recent advances exploring the molecular mechanisms governing the biological functions of CD100/Sema4D.Received 1 July 2003; received after revision 25 July 2003; accepted 29 July 2003 相似文献
15.
Decoding the Hedgehog signal in animal development 总被引:4,自引:0,他引:4
The Hedgehog (Hh) family of secreted proteins plays essential roles in a myriad of developmental processes via a complex signaling
cascade conserved in species ranging from insects to mammals. In many developmental contexts, Hh acts as long-range morphogen
to control distinct cellular outcomes as a function of its concentration. Here we review the current understanding of the
Hh signaling mechanisms that govern the establishment of the Hh gradient and the transduction of the Hh signal with an emphasis
on the intracellular signaling cascade from the receptor to the nuclear effector. We discuss how graded Hh signals are transduced
to govern distinct developmental outcomes.
Received 28 October 2005; received after revision 6 February 2006; accepted 15 February 2006 相似文献
16.
Human natural killer-1 (HNK-1) carbohydrate, comprising a unique trisaccharide HSO3-3GlcAβ1-3Galβ1-4GlcNAc, shows well-regulated expression and unique functions in the nervous system. Recent studies have revealed sophisticated and complicated expression mechanisms for HNK-1 glycan. Activities of biosynthetic enzymes are controlled through the formation of enzyme-complexes and regulation of subcellular localization. Functional aspects of HNK-1 carbohydrate were examined by overexpression, knockdown, and knockout studies of these enzymes. HNK-1 is involved in several neural functions such as synaptic plasticity, learning and memory, and the underlying molecular mechanisms have been illustrated upon identification of the target carrier glycoproteins of HNK-1 such as the glutamate receptor subunit GluA2 or tenascin-R. In this review, we describe recent findings about HNK-1 carbohydrate that provide further insights into the mechanism of its expression and function in the nervous system. 相似文献
17.
Forkhead transcription factors in immunology 总被引:5,自引:0,他引:5
18.
Mammalian lactoferrin (Lf) receptors are suggested to have pivotal roles for mediating multiple functions of Lf. In this review, we focus on current knowledge of the structure and function of mammalian Lf receptors, mainly the first cloned Lf receptor that has been shown to be expressed in the infant small intestine at high levels but also in virtually all other tissues. The small intestinal Lf receptor takes up iron from Lf into cells and presumably exerts other physiological functions. Other Lf receptors in various tissues have also been reported to mediate some functions of Lf, such as modulating immune function, inhibiting platelet aggregation and enhancing collagen gel contractile strength. The detailed mechanisms behind the receptor-Lf interactions still need to be elucidated. 相似文献
19.
DnaJ/Hsp40 (heat shock protein 40) proteins have been preserved throughout evolution and are important for protein translation,
folding, unfolding, translocation, and degradation, primarily by stimulating the ATPase activity of chaperone proteins, Hsp70s.
Because the ATP hydrolysis is essential for the activity of Hsp70s, DnaJ/Hsp40 proteins actually determine the activity of
Hsp70s by stabilizing their interaction with substrate proteins. DnaJ/Hsp40 proteins all contain the J domain through which
they bind to Hsp70s and can be categorized into three groups, depending on the presence of other domains. Six DnaJ homologs
have been identified in Escherichia coli and 22 in Saccharomyces cerevisiae. Genome-wide analysis has revealed 41 DnaJ/Hsp40 family members (or putative members) in humans. While 34 contain the typical
J domains, 7 bear partially conserved J-like domains, but are still suggested to function as DnaJ/ Hsp40 proteins. DnaJA2b,
DnaJB1b, DnaJC2, DnaJC20, and DnaJC21 are named for the first time in this review; all other human DnaJ proteins were dubbed
according to their gene names, e.g. DnaJA1 is the human protein named after its gene DNAJA1. This review highlights the progress
in studying the domains in DnaJ/Hsp40 proteins, introduces the mechanisms by which they interact with Hsp70s, and stresses
their functional diversity.
Received 27 April 2006; received after revision 5 June 2006; accepted 19 July 2006 相似文献
20.
Receptor communication within the lymphocyte plasma membrane: a role for the thrombospondin family of matricellular proteins 总被引:1,自引:0,他引:1
Lymphocytes, the principal cells of the immune system, carry out immune surveillance throughout the body by their unique capacity
to constantly reposition themselves between a free-floating vascular state and a tissue state characterized by migration and
frequent adhesive interactions with endothelial cells and components of the extracellular matrix. Therefore, mechanisms co-ordinating
adhesion and migration with signals delivered through antigen recognition probably play a pivotal role for the regulation
of lymphocyte behaviour and function. Endogenous thrombospondin-1 (TSP-1) seems to be the hub in such a mechanism for autocrine
regulation of T cell adhesion and migration. TSP-1 functions as a mediator of cis interaction of vital receptors within the T lymphocyte plasma membrane, including integrins, low density lipoprotein receptor-related
protein, calreticulin and integrin-associated protein.
Received 1 June 2006; received after revision 28 June 2006; accepted 11 October 2006 相似文献