Cell adhesion molecules, signal transduction and cell growth

Signals from dynamic cellular interactions between the extracellular matrix and neighboring cells ultimately input into the cellular decision-making process. These interactions form the basis of anchorage-dependent growth. Recent advances have provided the mechanistic details behind the ability of integrins, and other cell adhesion molecules (CAMs), to regulate both early signal transduction events initiated by soluble factors and downstream events more proximally involved in cell cycle progression. These actions appear to depend on the ability of CAMs to initiate the formation of organized structures that permit the efficient flow of information.     

Cell adhesion molecules: detection with univalent second antibody

Identification of cell surface molecules that play a role in cell-cell adhesion (here called cell adhesion molecules) has been achieved by demonstrating the inhibitory effect of univalent antibodies that bind these molecules in an in vitro assay of cell-cell adhesion. A more convenient reagent, intact (divalent) antibody, has been avoided because it might agglutinate the cells rather than blocking cell-cell adhesion. In this report, we show that intact rabbit immunoglobulin directed against certain cell surface molecules of Dictyostelium discoideum blocks cell-cell adhesion when the in vitro assay is performed in the presence of univalent goat anti-rabbit antibody. Under appropriate experimental conditions, the univalent second antibody blocks agglutination induced by the rabbit antibody without significantly interfering with its effect on cell-cell adhesion. This method promises to be useful for screening monoclonal antibodies raised against potential cell adhesion molecules because: (a) it allows for the screening of large numbers of antibody samples without preparation of univalent fragments; and (b) it requires much less antibody because of the greater affinity of divalent antibodies for antigens.     

Beta 1 integrins signal lipid second messengers required during cell adhesion.

Clustering of integrin receptors during cell adhesion stimulates signal transduction across the cell membrane. Second messengers are generated, activating cytosolic proteins and causing cytoskeletal assembly and rearrangement. HeLa cell adhesion to a collagen substrate has been shown to initiate an arachidonic acid-mediated signaling pathway, leading to the activation of protein kinase C (PKC) and cell spreading. To determine the role of integrin receptors in triggering this signaling pathway, monoclonal antibodies to beta 1 integrins were used to either cluster integrins on the cell surface or to provide an integrin-dependent substrate for cell adhesion. Using this approach, we have defined a pathway required for cell spreading that can be initiated by the ligation of integrins and leads to the activation of PKC. Specifically, our results indicate that clustering beta 1 integrins results in the activation of phospholipase A2 leading to the production of arachidonic acid and the activation of PKC.     

Neuropeptides, second messengers and insect molting

Insect molting is elicited by a class of polyhydroxylated steroids, ecdysteroids, that originate in the prothoracic glands. Ecdysteroid synthesis in the prothoracic glands is controlled in large measure by a peptide hormone from the brain, prothoracicotropic hormone (PTTH), which exists in two forms and is released into the general circulation as a result of environmental and developmental cues. The means by which PTTH activates the prothoracic glands has been examined at the cellular level and the data reveal the involvement of cAMP, calcium, calmodulin, cAMP-dependent protein kinase and the ultimate phosphorylation of a 34 kDa protein tentatively identified as ribosomal protein S6.     

Glucose metabolism, second messengers and insulin secretion

Insulin secretion from beta cells of the islets of Langerhans in the endocrine pancreas is regulated by glucose, glucose metabolites, metabolic intermediates such as ATP, acetyl CoA and reduced pyridine nucleotides, and classical second messengers. Receptor responses transduced by guanine nucleotide binding proteins modulate metabolic activity, the generation of second messengers, and cell depolarization during stimulus-response coupling in the beta cell. This review will consider insulin secretion as regulated by glucose metabolic pathways and second messengers.     

Phospholipidic second messengers and calcium

A number of signal molecules bind to surface receptors of target cells and generate intracellular messengers from inositol-containing phospholipids. The phosphatidyl inositol (4, 5) bisphosphate is hydrolyzed into inositol (1, 4, 5) trisphosphate and diacylglycerol. These messengers, via changes in the concentrations of cytosolic Ca2+ and H+ and/or protein phosphorylations, couple the signal to a variety of responses including activation of metabolism, secretion, aggregation, phototransduction, cell proliferation and possibly contraction.     

Cell adhesion molecules as tumour suppressors

Cell adhesion molecules, a diverse group of proteins expressed on the cell surface, have been implicated in numerous important cellular functions ranging from controlling morphogenesis to suppressing tumourigenesis. In this article, we discuss evidence supporting the idea that at least some proteins involved in cell adhesion may suppress tumourigenesis through influences on cell growth, differentiation and/or invasion. These studies suggest that some cell adhesion molecules may be encoded by tumour suppressor genes.     

Cell adhesion molecules and their subgroups in the nervous system.

Structural relationships among cell adhesion molecules have been used to classify two large families of these molecules into subgroups. The cell adhesion molecules within each subgroup share several structural features that indicate that they may function in similar or complementary ways either simultaneously or at different times and locations.     

Neural cell adhesion molecules influence second messenger systems

We have investigated the influence of the neural cell adhesion molecules L1 and N-CAM on second messenger systems using a PC12 rat pheochromocytoma cell line as a model and triggering cell surface receptors by specific antibody binding. Antibodies directed against L1 and N-CAM, but not against other cell surface components, reduce intracellular levels of the inositol phosphates IP2 and IP3, while intracellular levels of cAMP are unaffected. Antibodies against L1 and N-CAM also reduce intracellular pH and increase intracellular Ca2+ by opening Ca2+ channels in a pertussis toxin-inhibitable manner, suggesting the involvement of a G protein in the signal transduction process. Cross-linking of the adhesion molecules on the surface membrane is not required for the effects to occur. Furthermore, adhesion of single PC12 cells to each other elicits effects on intracellular pH and Ca2+ similar to those seen after application, underscoring the physiological significance of the observed changes.     

G-proteins and second messengers in mitogenesis

Growth factors stimulate mitogenesis via the generation of signal molecules or events. Transduction of these messages into the cell proceeds by the binding of the mitogen to a specific cell surface receptor which then stimulates the effector system (enzyme, ion channel, etc.) via a guanine nucleotide binding regulatory protein (G-protein). The specificity of a particular G-protein is a function of its unique α-subunit. This article reviews the effects of different growth factors upon second mesenger generation and discusses the involvement of the different G-proteins in these signal transduction pathways.     

人类胚胎植入过程中的细胞黏附分子(英文)

人类胚胎植入过程不仅受到在进化上保守的机制调节,而且也受到人类一种独有的机制调节。有证据显示,细胞黏附分子L-选择蛋白和trophinin在人类胚胎植入过程扮演独特的角色。在本文中,我们描述了L-选择素和trophinin的黏蛋白糖配体的双重作用,也描述了trophinin相关蛋白bystin和tastin的双重作用。我们随后描述了滋养外胚层细胞和子宫内膜上皮细胞中由trophinin调节的信号转导。本综述也涵盖了钙依粘连蛋白和整合素在人类胚胎植入过程中的作用。     

Cell adhesion molecules in stromal corneal dystrophies

The aim of the present study was to investigate the expression pattern of different cell adhesion molecules in corneal stromal dystrophies. Fifteen corneal buttons from patients diagnosed with three different types of stromal corneal dystrophies and healthy corneas were investigated. Paraffin embedded sections were stained immunohistochemically with monoclonal antibodies against human intercellular adhesion molecule-1 (ICAM-1), endothelial selectin (E-selectin) and endothelial cadherin (E-cadherin) using the avidin-biotin-peroxidase-complex technique. The sections were compared to normal eye bank controls. In corneas from granular dystrophy patients ICAM-1 was expressed focally in epithelial cells and in keratocytes, and expressed diffusely in endothelial cells. In corneas from macular dystrophy patients diffuse epithelial staining was observed and the stromal and endothelial expression was found to be similar to that of granular dystrophy. In lattice dystrophy, only the epithelial cells and endothelium were intensively positive for ICAM-1. E-selectin was not present on any layer of the corneal specimens. E-cadherin was observed only in the epithelium of all three types of corneal dystrophies. Normal corneas did not express any of the investigated adhesion molecules. We found different expression patterns of adhesion molecules in corneas from stromal dystrophies. Our results suggest that adhesion molecules may be involved in the pathogenesis of corneal stromal dystrophies.     

Intracellular second messengers mediate stress inducible hormesis and Programmed Cell Death: A review

Alterations in the levels of numerous second messengers are ubiquitous responses to all stresses that lead to apoptotic or hormetic responses. The sheer number and vast diversity of different second messenger systems activated in response to stresses belies a complexity that is often overlooked. This negligence is in large part due to the excessive focus on classical stress responsive second messenger mediators of stress especially Reactive Oxygen Species (ROS) but also others like calcium and ceramide. Here we review the many different intracellular second messengers that are involved in stress responses. We further integrate this information to emphasize that initial stress mediated responses consist of increased levels of a multitude of intracellular second messengers that serve to elicit the appropriate cell survival and/or cell death responses. We suggest that a greater focus on second messenger systems may shed more light on the processes that serve in the initiation of stress mediated PCD.     

Cell adhesion molecules in Drosophila synapse development and function

Synapse is a highly specialized inter-cellular structure between neurons or between a neuron and its target cell that mediates cell-cell communications. Ample results indicate that synaptic adhesion molecules are critically important in modulating the complexity and specificity of the synapse. And disruption of adhesive properties of synapses may lead to neurodevelopmental or neurodegenerative diseases. In this review, we will use the Drosophila NMJ as a model system for glutamatergic synapses to discuss the structure and function of homophilic and heterophilic synaptic adhesion molecules with special focus on recent findings in neurexins and neuroligins in Drosophila.