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1.
Phosphoinositides and signal transduction 总被引:17,自引:0,他引:17
Toker A 《Cellular and molecular life sciences : CMLS》2002,59(5):761-779
Phosphoinositides comprise a family of eight minor membrane lipids which play important roles in many signal transducing pathways in the cell. Signaling through various phosphoinositides has been shown to mediate cell growth and proliferation, apoptosis, cytoskeletal changes, insulin action and vesicle trafficking. A number of advances in signal transduction in the last decade has resulted in the discovery of a growing list of proteins which directly interact with high affinity and specificity with distinct phosphoinositides. Equally important, a number of phosphoinositide binding domains such as the pleckstrin homology domain have emerged as critical mediators of phosphoinositide signaling. Here, recent advances in phosphoinositide signaling are discussed. The aim of this review is to highlight particularly exciting advances made in the field over the last few years. The regulation of phosphoinositide metabolism by lipid kinases, phosphatases and phospholipases is reviewed, and considerable emphasis is placed on phosphoinositide-binding proteins. Finally, the role of these lipids in regulating signaling pathways and cell function is described. 相似文献
2.
Sphingolipids and glycosphingolipids are emerging as major players in many facets of cell physiology and pathophysiology.
We now present an overview of sphingolipid biochemistry and physiology, followed by a brief presentation of recent advances
in translational research related to sphingolipids. In discussing sphingolipid biochemistry, we focus on the structure of
sphingolipids, and their biosynthetic pathways – the recent identification of most of the enzymes in this pathway has led
to significant advances and better characterization of a number of the biosynthetic steps, and the relationship between them.
We then discuss some roles of sphingolipids in cell physiology, particularly those of ceramide and sphingosine-1-phosphate,
and mention current views about how these lipids act in signal transduction pathways. We end with a discussion of sphingolipids
and glycosphingolipids in the etiology and pathology of a number of diseases, such as cancer, immunity, cystic fibrosis, emphysema,
diabetes, and sepsis, areas in which sphingolipids are beginning to take a central position, even though many of the details
remain to be elucidated.
Received 13 February 2007; received after revision 19 April 2007; accepted 26 April 2007 相似文献
3.
T cell memory is a crucial feature of the adaptive immune system in the defense against pathogens. During the last years,
numerous studies have focused their efforts on uncovering the signals, inflammatory cues, and extracellular factors that support
memory differentiation. This research is beginning to decipher the complex gene network that controls memory programming.
However, how the different signals, that a T cell receives during the process of differentiation, interplay to trigger memory
programming is still poorly defined. In this review, we focus on the most recent advances in the field and discuss how T cell
receptor signaling and inflammation control CD8 memory differentiation. 相似文献
4.
Ling-Fei Zhang Shuai Jiang Mo-Fang Liu 《Cellular and molecular life sciences : CMLS》2017,74(16):2929-2941
The reprogramming of glucose metabolism from oxidative to glycolytic metabolism, known as the Warburg effect, is an anomalous characteristic of cancer cell metabolism. Recent studies have revealed a subset of microRNAs (miRNAs) that play critical roles in regulating the reprogramming of glucose metabolism in cancer cells. These miRNAs regulate cellular glucose metabolism by directly targeting multiple metabolic genes, including those encoding key glycolytic enzymes. In the first part of this review, we summarized the recent knowledge of miRNA regulation in the reprogramming of glucose metabolism in cancer cells and discussed the potential utilization of the key miRNA regulators as metabolic targets for developing new antitumor agents. Then, we summarized recent advances in methods and techniques for studying miRNA regulation in cancer cell metabolism. 相似文献
5.
Summary and conclusions The recent characterization of the human insulin receptor structure and its intrinsic tyrosine kinase activity represent major advances in our understanding of the mechanism of insulin action. It is reasonable to think that the insulin-induced autophosphorylation and activation of its receptor kinase represent an important event in the action of insulin on cell metabolism and growth. The fundamental research reviewed may be followed by the discovery of molecular receptor defects in clinical syndromes of insulin resistance. 相似文献
6.
The recent characterization of the human insulin receptor structure and its intrinsic tyrosine kinase activity represent major advances in our understanding of the mechanism of insulin action. It is reasonable to think that the insulin-induced autophosphorylation and activation of its receptor kinase represent an important event in the action of insulin on cell metabolism and growth. The fundamental research reviewed may be followed by the discovery of molecular receptor defects in clinical syndromes of insulin resistance. 相似文献
7.
Collective cell movement is one of the strategies for achieving the complex shapes of tissues and organs. In this process, multiple cells within a group held together by cell–cell adhesion acquire mobility and move together in the same direction. In some well-studied models of collective cell movement, the mobility depends strongly on traction generated at the leading edge by cells located at the front. However, recent advances in live-imaging techniques have led to the discovery of other types of collective cell movement lacking a leading edge or even a free edge at the front, in a diverse array of morphological events, including tubule elongation, epithelial sheet extension, and tissue rotation. We herein review some of the developmental events that are organized by collective cell movement and attempt to elucidate the underlying cellular and molecular mechanisms, which include membrane protrusions, guidance cues, cell intercalation, and planer cell polarity, or chirality pathways. 相似文献
8.
The cellular functions of clathrin 总被引:3,自引:0,他引:3
Royle SJ 《Cellular and molecular life sciences : CMLS》2006,63(16):1823-1832
Membranes and proteins are moved around the cell in small vesicles. A protein coat aids the budding of such vesicles from
donor membranes. The major type of coat used by the cell is composed of clathrin, a three-legged protein that can form lattice-like
coats on membranes destined for trafficking. In this review, I outline what we know about clathrin and discuss some recent
advances in understanding the basic biology of this fascinating molecule, which include building a molecular model of a clathrin
lattice and discovery of a new function for clathrin that occurs during mitosis.
Received 12 December 2005; received after revision 21 March 2006; accepted 29 March 2006 相似文献
9.
Wolfrum C 《Cellular and molecular life sciences : CMLS》2007,64(19-20):2465-2476
Translation of nutrient stimuli through intracellular signaling is important for adaptation and regulation of metabolic processes, while deregulation by either genetic or environmental factors predisposes towards the development of metabolic disorders. Besides providing energy, fatty acids act as prominent signaling molecules by altering cell membrane structures, affecting the lipid modification status of proteins, and by modulating ligand-activated nuclear receptor activity. Given their highly hydrophobic nature, fatty acids in the aqueous intracellular compartment are bound to small intracellular lipid binding proteins which function as intracellular carriers of these hydrophobic components. This review describes recent advances in identifying intracellular pathways for cytosolic fatty acid signaling through ligand activated receptors by means of small intracellular lipid binding proteins. The mechanism behind intracellular fatty acid transport and subsequent nuclear receptor activation is an emerging concept, and advances in understanding this process provide new potential therapeutic targets towards the treatment of metabolic disorders. 相似文献
10.
The vasculature is one of the most dynamic tissues that encounter numerous mechanical cues derived from pulsatile blood flow, blood pressure, activity of smooth muscle cells in the vessel wall, and transmigration of immune cells. The inner layer of blood and lymphatic vessels is covered by the endothelium, a monolayer of cells which separates blood from tissue, an important function that it fulfills even under the dynamic circumstances of the vascular microenvironment. In addition, remodeling of the endothelial barrier during angiogenesis and trafficking of immune cells is achieved by specific modulation of cell–cell adhesion structures between the endothelial cells. In recent years, there have been many new discoveries in the field of cellular mechanotransduction which controls the formation and destabilization of the vascular barrier. Force-induced adaptation at endothelial cell–cell adhesion structures is a crucial node in these processes that challenge the vascular barrier. One of the key examples of a force-induced molecular event is the recruitment of vinculin to the VE-cadherin complex upon pulling forces at cell–cell junctions. Here, we highlight recent advances in the current understanding of mechanotransduction responses at, and derived from, endothelial cell–cell junctions. We further discuss their importance for vascular barrier function and remodeling in development, inflammation, and vascular disease. 相似文献
11.
Aging clock: the watchmaker’s masterpiece 总被引:1,自引:0,他引:1
Ishikawa F 《Cellular and molecular life sciences : CMLS》2000,57(5):698-704
The phenomenon of cellular senescence has been known for almost four decades. Yet, until very recently, the molecular mechanisms that lead to senescence have been poorly understood. However, substantial progress has been made in the last few years toward identifying the pathways executing senescence. This r view focuses on two major advances in this field, the telomere aging clock theory and the cell cycle regulatory mechanisms in senescent cells. These recent studies indicate that cellular senescence is a highly elaborate and active process, which presumably works as an anti-oncogenic mechanism. 相似文献
12.
Chemokines are a vertebrate-specific group of small molecules that regulate cell migration and behaviour in diverse contexts.
So far, around 50 chemokines have been identified in humans, which bind to 18 different chemokine receptors. These are members
of the seven-transmembrane receptor family. Initially, chemokines were identified as modulators of the immune response. Subsequently,
they were also shown to regulate cell migration during embryonic development. Here, we discuss the influence of chemokines
and their receptors on angiogenesis, or the formation of new blood vessels. We highlight recent advances in our understanding
of how chemokine signalling might directly influence endothelial cell migration. We furthermore examine the contributions
of chemokine signalling in immune cells during this process. Finally, we explore possible implications for disease settings,
such as chronic inflammation and tumour progression. 相似文献
13.
Advances in our understanding of cardiac development have fuelled research into cellular approaches to myocardial repair of
the damaged heart. In this collection of reviews we present recent advances into the basic mechanisms of heart development
and the resident and non-resident progenitor cell populations that are currently being investigated as potential mediators
of cardiac repair. Together these reviews illustrate that despite our current knowledge about how the heart is constructed,
caution and much more research in this exciting field is essential. The current momentum to evaluate the potential for cardiac
repair will in turn accelerate research into fundamental aspects of myocardial biology. 相似文献
14.
15.
Carosella ED Gregori S Rouas-Freiss N LeMaoult J Menier C Favier B 《Cellular and molecular life sciences : CMLS》2011,68(3):353-368
The non-classical HLA class I molecule HLA-G was initially shown to play a major role in feto–maternal tolerance. Since this
discovery, it has been established that HLA-G is a tolerogenic molecule which participates to the control of the immune response.
In this review, we summarize the recent advances on (1) the multiple structures of HLA-G, which are closely associated with
their role in the inhibition of NK cell cytotoxicity, (2) the factors that regulate the expression of HLA-G and its receptors,
(3) the mechanism of action of HLA-G at the immunological synapse and through trogocytosis, and (4) the generation of suppressive
cells through HLA-G. Moreover, we also review recent findings on the non-immunological functions of HLA-G in erythropoiesis
and angiogenesis. 相似文献
16.
Samantha R. Oakes David Gallego-Ortega Christopher J. Ormandy 《Cellular and molecular life sciences : CMLS》2014,71(22):4301-4324
Advances in the study of hematopoietic cell maturation have paved the way to a deeper understanding the stem and progenitor cellular hierarchy in the mammary gland. The mammary epithelium, unlike the hematopoietic cellular hierarchy, sits in a complex niche where communication between epithelial cells and signals from the systemic hormonal milieu, as well as from extra-cellular matrix, influence cell fate decisions and contribute to tissue homeostasis. We review the discovery, definition and regulation of the mammary cellular hierarchy and we describe the development of the concepts that have guided our investigations. We outline recent advances in in vivo lineage tracing that is now challenging many of our assumptions regarding the behavior of mammary stem cells, and we show how understanding these cellular lineages has altered our view of breast cancer. 相似文献
17.
Vascular integrins: pleiotropic adhesion and signaling molecules in vascular homeostasis and angiogenesis 总被引:11,自引:0,他引:11
New blood vessel formation, a process referred to as angiogenesis, is essential for embryonic development and for many physiological and pathological processes during postnatal life, including cancer progression. Endothelial cell adhesion molecules of the integrin family have emerged as critical mediators and regulators of angiogenesis and vascular homeostasis. Integrins provide the physical interaction with the extracellular matrix necessary for cell adhesion, migration and positioning, and induction of signaling events essential for cell survival, proliferation and differentiation. Antagonists of integrin alpha V beta 3 suppress angiogenesis in many experimental models and are currently tested in clinical trials for their therapeutic efficacy against angiogenesis-dependent diseases, including cancer. Furthermore, interfering with signaling pathways downstream of integrins results in suppression of angiogenesis and may have relevant therapeutic implications. In this article we review the role of integrins in endothelial cell function and angiogenesis. In the light of recent advances in the field, we will discuss their relevance as a therapeutic target to suppress tumor angiogenesis. 相似文献
18.
Frank W. Pfrieger 《Cellular and molecular life sciences : CMLS》2009,66(13):2037-2047
Brain function relies on communication among neurons via highly specialized contacts, the synapses, and synaptic dysfunction lies at the heart of age-, disease-, and injury-induced defects of the nervous system. For these reasons, the formation—and repair—of synaptic connections is a major focus of neuroscience research. In this review, I summarize recent evidence that synapse development is not a cell-autonomous process and that its distinct phases depend on assistance from the so-called glial cells. The results supporting this view concern synapses in the central nervous system as well as neuromuscular junctions and originate from experimental models ranging from cell cultures to living flies, worms, and mice. Peeking at the future, I will highlight recent technical advances that are likely to revolutionize our views on synapse–glia interactions in the developing, adult and diseased brain. 相似文献
19.
The Usher syndrome, an autosomal recessive deafness and blindness, is genetically and clinically heterogeneous. In the past 4 years, genes mutated in Usher syndrome type Ib and type IIa have been described. The Usher Ib gene encodes the motor protein myosin VIIa and was identified as the human homolog of the mouse shaker-1 gene. The Usher type IIa gene was identified by positional cloning and encodes a protein with homology to extracellular matrix proteins and cell adhesion molecules. This review summarizes the current knowledge regarding both the genetic and molecular aspects of Usher syndrome in the context of recent scientific advances in the areas of sensorineural deafness and retinitis pigmentosa. 相似文献
20.
Alastair S. Robertson Elizabeth Smythe Kathryn R. Ayscough 《Cellular and molecular life sciences : CMLS》2009,66(13):2049-2065
Endocytosis is a fundamental eukaryotic process required for remodelling plasma-membrane lipids and protein to ensure appropriate
membrane composition. Increasing evidence from a number of cell types reveals that actin plays an active, and often essential,
role at key endocytic stages. Much of our current mechanistic understanding of the endocytic process has come from studies
in budding yeast and has been facilitated by yeast’s genetic amenability and by technological advances in live cell imaging.
While endocytosis in metazoans is likely to be subject to a greater array of regulatory signals, recent reports indicate that
spatiotemporal aspects of vesicle formation requiring actin are likely to be conserved across eukaryotic evolution. In this
review we focus on the ‘modular’ model of endocytosis in yeast before highlighting comparisons with other cell types. Our
discussion is limited to endocytosis involving clathrin as other types of endocytosis have not been demonstrated in yeast. 相似文献