共查询到20条相似文献,搜索用时 46 毫秒
1.
Microtubules are fibrous elements in the cytoplasm of eukaryotic cells, where they perform a wide variety of functions. Microtubules
are major organizers of the cell interior and are vitally involved in motility events such as chromosome migration during
cell division. To fulfill their physiological function, microtubule arrays have to undergo dramatic changes in their spatial
arrangement, and this depends to a large extent on the complex and special dynamic properties of the individual polymers.
In this review we first describe the intrinsic dynamic properties of microtubules assembled in vitro from purified tubulin
and examine the relationships between these properties and microtubule functions. Subsequent sections concern microtubule
dynamics in vivo, their similarity and differences with microtubule dynamics in vitro, and the nature of the cellular regulators
which act on microtubule assemblies in physiological conditions.
Received 2 May 2001; received after revision 10 July 2001; accepted 10 July 2001 相似文献
2.
Molecular paleontology 总被引:3,自引:0,他引:3
Molecular paleontology, i.e., the recovery of DNA from ancient human, animal, and plant remains is an innovative research
field that has received progressively more attention from the scientific community since the 1980s. In the last decade, the
field was punctuated by claims which aroused great interest but eventually turned out to be fakes - the most famous being
the sequence of dinosaur DNA later shown to be of human origin. At present, the discipline is characterized by some certainties
and many doubts. We know, for example, that we have reasonable chances to recover authentic DNA from a mammoth carcass, while
our chances are negligible (or nonexistent) in the case of a dynastic mummy from Egypt. On the other hand, though we are developing
convincing models of DNA decay in bone, we are not yet able to predict whether a certain paleontological or archeological
site will yield material amenable to DNA analysis. This article reviews some of the most important and promising investigations
using molecular paleontology approaches, such as studies on the conservation of DNA in human bone, the quest for ancient DNA
in permafrost-frozen fauna, the Tyrolean iceman, and the Neandertals.
Received 5 April 2001; received after revision 5 July 2001; accepted 5 July 2001 相似文献
3.
Molina H 《Cellular and molecular life sciences : CMLS》2002,59(2):220-229
Complement has an important role in inflammation and in the normal function of the immune system. Activated complement fragments
have the capacity to bind and damage self-tissues. Cells from vertebrates express on their surface regulators of complement
activation that protect them from the deleterious effects of cell-bound complement fragments. Abnormalities in these regulators
of complement activation may participate in the pathogenesis of autoimmune diseases and inflammatory disorders. Murine Crry
is one of these regulators that inhibits the activation of the third component of complement and protects self-tissues from
complement-mediated damage. Experimental work on Crry has increased our understanding of the immunobiology of complement regulation
and the potential role of complement and complement inhibitors in the development and treatment of human diseases.
Received 13 June 2001; received after revision 12 July 2001; accepted 9 August 2001 相似文献
4.
Ernfors P 《Cellular and molecular life sciences : CMLS》2001,58(8):1036-1044
Neurotrophic factors are present in limiting quantities, and neurons that obtain an adequate supply of the required neurotrophic
factor survive whereas those that compete unsuccessfully die. Analysis of null mutant mice for neurotrophins and Trk receptors
as well as in vivo experiments in ovo in the chick applying exogenous neurotrophins or neutralising antisera have significantly
increased knowledge of the roles they play during development. This review focuses on recent advances in understanding the
various roles of neurotrophins in dorsal root ganglion sensory neuron development at different times in embryonic development
- an early local role for differentiation of the sensory precursor cells and a later survival-promoting target-derived role
for the mature neurons. Neurotrophic factors are present in limiting quantities, and neurons that obtain an adequate supply
of the required neurotrophic factor survive whereas those that compete unsuccessfully die. Analysis of null mutant mice for
neurotrophins and Trk receptors as well as in vivo experiments in ovo in the chick applying exogenous neurotrophins or neutralising
antisera have significantly increased knowledge of the roles they play during development. This review focuses on recent advances
in understanding the various roles of neurotrophins in dorsal root ganglion sensory neuron development at different times
in embryonic development - an early local role for differentiation of the sensory precursor cells and a later survival-promoting
target-derived role for the mature neurons. 相似文献
5.
6.
Neurotrophin signalling pathways regulating neuronal apoptosis 总被引:18,自引:0,他引:18
Recent evidence indicates that naturally occurring neuronal death in mammals is regulated by the interplay between receptor-mediated prosurvival and proapoptotic signals. The neurotrophins, a family of growth factors best known for their positive effects on neuronal biology, have now been shown to mediate both positive and negative survival signals, by signalling through the Trk and p75 neurotrophin receptors, respectively. The mechanisms whereby these two neurotrophin receptors interact to determine neuronal survival have been difficult to decipher, largely because both can signal independently or coincidentally, depending upon the cell or developmental context. Nonetheless, the past several years have seen significant advances in our understanding of this receptor signalling system. In this review, we focus on the proapoptotic actions of the p75 neurotrophin receptor (p75NTR), and on the interplay between Trk and p75NTR that determines neuronal survival. 相似文献
7.
Erika Gucciardo Nami Sugiyama Kaisa Lehti 《Cellular and molecular life sciences : CMLS》2014,71(19):3685-3710
The erythropoietin-producing hepatocellular (Eph) receptors comprise the largest family of receptor tyrosine kinases (RTKs). Initially regarded as axon-guidance and tissue-patterning molecules, Eph receptors have now been attributed with various functions during development, tissue homeostasis, and disease pathogenesis. Their ligands, ephrins, are synthesized as membrane-associated molecules. At least two properties make this signaling system unique: (1) the signal can be simultaneously transduced in the receptor- and the ligand-expressing cell, (2) the signaling outcome through the same molecules can be opposite depending on cellular context. Moreover, shedding of Eph and ephrin ectodomains as well as ligand-dependent and -independent receptor crosstalk with other RTKs, proteases, and adhesion molecules broadens the repertoire of Eph/ephrin functions. These integrated pathways provide plasticity to cell–microenvironment communication in varying tissue contexts. The complex molecular networks and dynamic cellular outcomes connected to the Eph/ephrin signaling in tumor–host communication and stem cell niche are the main focus of this review. 相似文献
8.
Paneth cells (PCs) were described over a century ago as granulated cells located at the base of small intestinal crypts,
the 'crypts of Lieberkühn.' Various histochemical staining procedures were developed that identified PCs based on their distinctive
granule staining pattern. Early on, PCs were proposed to perform a specialized function other than absorption of digested
nutrients, the predominant task of the small intestinal epithelium. Since then, many constituents of the PC granules have
been biochemically characterized. The presence of various granule-associated antimicrobial substances and their release upon
microbial challenge suggest that PCs function as specialized defense cells in the small intestine. Altered resistance to microbial
infection in animal models with disrupted or augmented PC function provides further support for the host defense role of PCs.
Other PC components suggest that PCs may also participate in the regulation of lumenal ionic composition, crypt development,
digestion, and intestinal inflammation.
Received 6 June 2001; received after revision 26 July 2001; accepted 27 July 2001 相似文献
9.
Signalling roles of mammalian phospholipase D1 and D2 总被引:11,自引:0,他引:11
S. Cockcroft 《Cellular and molecular life sciences : CMLS》2001,58(11):1674-1687
Phospholipase D (PLD) catalyses the hydrolysis of phosphatidylcholine to generate the lipid second messenger, phosphatidate
(PA) and choline. PLD activity in mammalian cells is low and is transiently stimulated upon activation by G-protein-coupled
and receptor tyrosine kinase cell surface receptors. Two mammalian PLD enzymes (PLD1 and PLD2) have been cloned and their
intracellular regulators identified as ARF and Rho proteins, protein kinase Cα as well as the lipid, phosphatidylinositol
[4, 5] bisphosphate (PIP2). I discuss the regulation of these enzymes by cell surface receptors, their cellular localisation and the potential function
of PA as a second messenger. Evidence is presented for a role of PA in regulating the lipid kinase activity of PIP 5-kinase,
an enzyme that synthesises PIP2. A signalling role of phospholipase D via PA and indirectly via PIP2 in regulating membrane traffic and actin dynamics is indicated by the available data.
Received 25 April 2001; received after revision 15 June 2001; accepted 15 June 2001 相似文献
10.
Neurotrophins are growth factors implicated in the development and maintenance of different neuronal populations in the nervous system. Neurotrophins bind to two sets of receptors, Trk receptor tyrosine kinases and the p75NTR receptor, to activate several different signaling pathways that mediate various biological functions. While Trk receptor activation has been well-studied and triggers the well-characterized Ras/Rap-MAPK, PI3K-Akt, and PLCgamma-PKC cascades, p75NTR signaling is more complex, and its in vivo significance has not yet been completely determined. In the last few years, p75NTR has received much attention mainly due to recent findings describing pro-neurotrophins as new ligands for the receptor and the ability of the receptor to form different complexes with other transmembrane proteins. This review will update the neurotrophin signaling pathways known for Trk receptors to include newly identified Trk-interacting molecules and will address surprising new findings that suggest a role for p75NTR in different receptor complexes and functions. 相似文献
11.
Receptor binding, internalization, and retrograde transport of neurotrophic factors 总被引:15,自引:0,他引:15
This review deals with the receptor interactions of neurotrophic factors, focusing on the neurotrophins of the nerve growth
factor (NGF) family, the glial cell derived neurotrophic factor (GDNF) family, and the ciliary neurotrophic factor (CNTF)
family. The finding that two proteins, p75NTR and Trk, act as receptors for NGF in neurons generated the discovery of other neurotrophic factors/receptor families and
has enhanced our understanding of the development, survival, regeneration, and degeneration of the nervous system. The kinetics
of binding, the structure of the ligand-receptor complex, and the mechanism of retrograde transport of the neurotrophins are
discussed in detail and compared to information available on the GDNF and CNTF families. Each neurotrophic factor family,
i.e., NGF, GDNF, and CNTF, has a set of receptors with specificity for individual members of the family and a common receptor
without member specificity that, in some families, generates the cellular signal and retrograde transport. 相似文献
12.
The mitochondrial PHB complex: roles in mitochondrial respiratory complex assembly, ageing and degenerative disease 总被引:16,自引:0,他引:16
Nijtmans LG Artal SM Grivell LA Coates PJ 《Cellular and molecular life sciences : CMLS》2002,59(1):143-155
Although originally identified as putative negative regulators of the cell cycle, recent studies have demonstrated that the
PHB proteins act as a chaperone in the assembly of subunits of mitochondrial respiratory chain complexes. The two PHB proteins,
Phb1p and Phb2p, are located in the mitochondrial inner membrane where they form a large complex that represents a novel type
of membrane-bound chaperone. On the basis of its native molecular weight, the PHB-complex should contain 12-14 copies of both
Phb1p and Phb2p. The PHB complex binds directly to newly synthesised mitochondrial translation products and stabilises them
against degradation by membrane-bound metalloproteases belonging to the family of mitochondrial triple-A proteins. Sequence
homology assigns Phb1p and Phb2p to a family of proteins which also contains stomatins, HflKC, flotillins and plant defence
proteins. However, to date only the bacterial HflKC proteins have been shown to possess a direct functional homology with
the PHB complex. Previously assigned actions of the PHB proteins, including roles in tumour suppression, cell cycle regulation,
immunoglobulin M receptor binding and apoptosis seem unlikely in view of any hard evidence in their support. Nevertheless,
because the proteins are probably indirectly involved in ageing and cancer, we assess their possible role in these processes.
Finally, we suggest that the original name for these proteins, the prohibitins, should be amended to reflect their roles as
proteins that hold badly formed subunits, thereby keeping the nomenclature already in use but altering its meaning to reflect
their true function more accurately.
Received 21 May 2001; received after revision 2 July 2001; accepted 24 July 2001 相似文献
13.
Axonal transport of neurofilaments in normal and disease states 总被引:5,自引:0,他引:5
Miller CC Ackerley S Brownlees J Grierson AJ Jacobsen NJ Thornhill P 《Cellular and molecular life sciences : CMLS》2002,59(2):323-330
Neurofilaments are among the most abundant organelles in neurones. They are synthesised in cell bodies and then transported
into and through axons by a process termed 'slow axonal transport' at a rate that is distinct from that driven by conventional
fast motors. Several recent studies have now demonstrated that this slow rate of transport is actually the consequence of
conventional fast rates of movement that are interrupted by extended pausing. At any one time, most neurofilaments are thus
stationary. Accumulations of neurofilaments are a pathological feature of several human neurodegenerative diseases suggesting
that neurofilament transport is disrupted in disease states. Here, we review recent advances in our understanding of neurofilament
transport in both normal and disease states. Increasing evidence suggests that phosphorylation of neurofilaments is a mechanism
for regulating their transport properties, possibly by promoting their detachment from the motor(s). In some neurodegenerative
diseases, signal transduction mechanisms involving neurofilament kinases and phosphatases may be perturbed leading to disruption
of transport.
Received 11 July 2001; received after revision 30 August 2001; accepted 31 August 2001 相似文献
14.
Signalling in viral entry 总被引:9,自引:0,他引:9
Greber UF 《Cellular and molecular life sciences : CMLS》2002,59(4):608-626
Viral infections are serious battles between pathogens and hosts. They can result in cell death, elimination of the virus
or latent infection keeping both cells and pathogens alive. The outcome of an infection is often determined by cell signalling.
Viruses deliver genomes and proteins with signalling potential into target cells and thereby alter the metabolism of the host.
Virus interactions with cell surface receptors can elicit two types of signals, conformational changes of viral particles,
and intracellular signals triggering specific cellular reactions. Responses by cells include stimulation of innate and adaptive
immunity, growth, proliferation, survival and apoptosis. In addition, virus-activated cell signalling boosts viral entry and
gene delivery, as recently shown for adenoviruses and adeno-associated viruses. This review illustrates that multiple activation
of host cells during viral entry profoundly impacts the elaborate relationship between hosts and viral pathogens.
Received 13 September 2001; received after revision 23 October 2001; accepted 16 November 2001 相似文献
15.
CD23 (the low-affinity IgE receptor) as a C-type lectin: a multidomain and multifunctional molecule 总被引:5,自引:0,他引:5
Kijimoto-Ochiai S 《Cellular and molecular life sciences : CMLS》2002,59(4):648-664
This review, regards the low-affinity receptor CD23 as a C-type lectin and compares it with other C-type lectins and C-type
lectin-like receptors. C-type lectins such as the asialoglycoprotein receptor, as well as the dendritic cell immunoreceptor
and the dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin on dendritic cell lectin, possess amino
acid sequences which interact with Ca++ and sugar, and many of them possess an endocytosis signal sequence that includes tyrosine or serine in the cytoplasmic region.
In contrast, natural killer receptors lack the Ca++ and sugar-binding amino acids but conserve homologous cysteines in the form of C-type lectin, and possess an immunoreceptor
tyrosine-based inhibitory motif in the cytoplasmic region which inhibits killer activity when they recognize the self major
histocompatibility (MHC) class I molecule. Since human CD23a form has a similar amino acid sequence, the possibility that
this sequence is an endocytosis signal or an ITIM is discussed. The function of the reverse RGD and RGD-binding inhibitory
peptide in human CD23 from the point of view of the relation between a C-type lectin and MHC class II molecules is also considered.
Received 21 May 2001; received after revision 28 November 2001; accepted 29 November 2001 相似文献
16.
17.
Davoli C Marconi A Serafino A Iannoni C Marcheggiano A Ravagnan G 《Cellular and molecular life sciences : CMLS》2002,59(3):527-539
Nerve growth factor (NGF) belongs by sequence homology to the neurotrophins, a family of proteins binding the same p75 receptor
and closely related members of the Trk family of receptor tyrosine kinases. Fundamental in the vertebrate nervous system,
neurotrophin signals have also been suggested as essential for relatively complex nervous systems occurring in invertebrate
species that live longer than Caenorhabditis elegans and Drosophila melanogaster. Mammalian neurotrophins have been found to influence invertebrate neuronal growth. However, there are only a few data on
the presence of molecules related to neurotrophin signalling components in invertebrates. Our studies provide evidence that
analogues of neurotrophins and neurotrophin receptors are expressed in Eisenia foetida earthworms. In particular, NGF-like and Trk-like immunoreactive proteins are both expressed in the nervous system, whereas
p75-like positivity identifies tubular structures associated with dorsal pores that are involved in the earthworm response
to mechanical irritation or stress.
Received 12 November 2001; received after revision 8 January 2002; accepted 8 January 2002 相似文献
18.
Franciosi S 《Cellular and molecular life sciences : CMLS》2001,58(7):921-930
α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptors are one type of ionotropic glutamate receptor involved
in rapid excitatory synaptic transmission. AMPA receptors have been increasingly implicated in long-term potentiation, and
recent evidence suggests that they may play a role in disorders affecting the nervous system. The finding that early in postnatal
development AMPA receptors are not expressed has lately been the focus of much attention. Resolving the factors involved in
AMPA receptor expression suggests that their induction is a developmentally regulated process with the possibility that alterations
in receptor expression may be correlated with pathology in neurological disorders. This paper provides an overview of factors
involved in AMPA receptor induction as well as of their role in plasticity and neuronal pathologies.
Received 5 December 2000; received after revision 12 January 2001; accepted 2 February 2001 相似文献
19.
Kopp P 《Cellular and molecular life sciences : CMLS》2001,58(9):1301-1322
The thyrotropin (TSH) receptor plays a preeminent role in thyroid physiology and disease. TSH, acting through the TSH receptor,
is the major stimulator of thyroid cell growth, differentiation and function. In Graves' disease, the TSH receptor is the
target of stimulating antibodies that cause hyperthyroidism. Although still a topic of debate, the TSH receptor has been implicated
in the pathogenesis of the endocrine ophthalmopathy associated with Graves' disease. Blocking antibodies against the TSH receptor
are involved in the development of hypothyroidism in a subset of patients with autoimmune hypothyroidism. Transplacental passage
of stimulating or blocking TSH receptor antibodies from a mother with autoimmune thyroid disease may result in transient hyper-
or hypothyroidism in early infancy. During pregnancy, the placental hormone human choriogonadotropin (hCG) can cause gestational
hyperthyroidism through cross-reaction with the TSH receptor. Gestational hyperthyroidism may also be involved in the pathogenesis
of hyperemesis gravidarum. Trophoblast tumors secreting hCG are a rare cause of hyperthyroidism. Somatic activating mutations
of the TSH receptor have been identified as a molecular cause of toxic adenomas, whereas activating mutations in the germline
give rise to nonautoimmune familial hyperthyroidism or sporadic congenital hyperthyroidism. These gain-of-function mutations
are dominant, and one mutated allele is sufficient to result in disease. Inactivating germline mutations of both TSH receptor
alleles lead to variable degrees of resistance to TSH, encompassing a spectrum ranging from euthyroid hyperthyrotropinemia
to overt hypothyroidism with thyroid hypoplasia.
Received 31 January 2001; received after revision 3 April 2001; accepted 3 April 2001 相似文献
20.
Sphingolipids in mammalian cell signalling 总被引:12,自引:0,他引:12
Sphingolipids and their metabolites, ceramide, sphingosine and sphingosine-1-phosphate, are involved in a variety of cellular
processes including differentiation, cellular senescence, apoptosis and proliferation. Ceramide is the main second messenger,
and is produced by sphingomyelinase-induced hydrolysis of sphingomyelin and by de novo synthesis. Many stimuli, e.g. growth
factors, cytokines, G protein-coupled receptor agonists and stress (UV irradiation) increase cellular ceramide levels. Sphingomyelin
in the plasma membrane is located primarily in the outer (extracellular) leaflet of the bilayer, whilst sphingomyelinases
are found at the inner (cytosolic) face and within lysosomes/endosomes. Such cellular compartmentalisation restricts the site
of ceramide production and subsequent interaction with target proteins. Glycosphingolipids and sphingomyelin together with
cholesterol are major components of specialised membrane microdomains known as lipid rafts, which are involved in receptor
aggregation and immune responses. Many signalling molecules, for example Src family tyrosine kinases and glycosylinositolphosphate-anchored
proteins, are associated with rafts, and disruption of these domains affects cellular responses such as apoptosis. Sphingosine
and sphingosine-1-phosphate derived from ceramide are also signalling molecules. In particular, sphingosine-1-phosphate is
involved in proliferation, differentiation and apoptosis. Sphingosine-1-phosphate can act both extracellularly through endothelial-differentiating
gene (EDG) family G protein-coupled receptors and intracellularly through direct interactions with target proteins. The importance
of sphingolipid signalling in cardiovascular development has been reinforced by recent reports implicating EDG receptors in
the regulation of embryonic cardiac and vascular morphogenesis.
Received 16 May 2001; received after revision 29 June 2001; accepted 3 July 2001 相似文献