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Query: UNIPROT:P06889 (Mol)
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The intercellular adhesion molecule (ICAM) 1 is an Ig-like cell adhesion molecule expressed by several cell types, including leukocytes and endothelial cells. It can be induced in a cell-specific manner by several cytokines, for example, tumor necrosis factor-alpha, interleukin-1, and interferon-gamma, and inhibited by glucocorticoids. Its ligands are the membrane-bound integrin receptors LFA-1 and Mac-1 on leukocytes, CD43, the soluble molecule fibrinogen, the matrix factor hyaluronan, rhinoviruses, and Plasmodium falciparum malaria-infected erythrocytes. ICAM-1 expression is predominantly transcriptionally regulated. The ICAM-1 promoter contains several enhancer elements, among them a novel kappa B element which mediates effects of 12-O-tetradecanoylphorbol-13-acetate, interleukin-1, lipopolysaccharide, tumor necrosis factor-alpha, and glucocorticoids. Expression regulation is cell specific and depends on the availability of cytokine/hormone receptors, signal transduction pathways, transcription factors, and posttranscriptional modification. ICAM-1 plays a role in inflammatory processes and in the T-cell mediated host defense system. It functions as a costimulatory molecule on antigen-presenting cells to activate MHC class II restricted T-cells, and on other cell types in association with MHC class I to activate cytotoxic T-cells. ICAM-1 on endothelium plays an important role in migration of (activated) leukocytes to sites of inflammation. ICAM-1 is shed by the cell and detected in plasma as sICAM-1. Regulation and significance of sICAM-1 are as yet unclear, but sICAM-1 is increased in many pathological conditions. ICAM-1 may play a pathogenetic role in rhinovirus infections. Derangement of ICAM-1 expression probably contributes to the clinical manifestations of a variety of diseases, predominantly by interfering with normal immune function. Among these are malignancies (e.g., melanoma and lymphomas), many inflammatory disorders (e.g., asthma and autoimmune disorders), atherosclerosis, ischemia, certain neurological disorders, and allogeneic organ transplantation. Interference with ICAM-1 leukocyte interaction using mAbs, soluble ICAM-1, antisense ICAM-1 RNA, and in the case of melanoma mAb-coupled immunotoxin, may offer therapeutic possibilities in the future. Integration of knowledge concerning membrane-bound and soluble ICAM-1 into a single functional system is likely to contribute to elucidating the immunoregulatory function of ICAM-1 and its pathophysiological significance in various disease entities.
J Mol Med (Berl) 1996 Jan
PMID:Intercellular adhesion molecule-1. 883 67

A spontaneously established porcine granulosa cell line (PGC-2) was cloned through the continuous culturing of primary granulosa cells collected from equine chorionic gonadotropin (eCG)-treated prepubertal gilts. This established cell line has undergone approximately 100 passages and shows contact-inhibition of growth. PGC-2 stained with a monoclonal antibody (mAb) directed against cytokeratin, indicating its epithelial nature, but not with a mAb directed against vimentin, suggesting that it is not fibroblast-derived. Immunoblotting revealed that PGC-2 expresses cadherin, an epithelial Ca+2-dependent cell adhesion molecule. The cells were dependent on serum for growth and had a doubling time of approximately 20 hr when cultured with 10% fetal bovine serum. The cell line was examined for the presence of FSH receptors, cAMP responses, and steroidogenic capabilities. The cell line lacks FSH receptors as assessed by radiolabelled-ligand binding, and no transcripts for FSH receptor were detected by Northern blotting of total cellular RNA. Neither FSH nor cholera toxin (0.5 ng/mL) stimulated increases in cAMP levels in these cells, whereas forskolin (10 microM) induced a fivefold increase in cAMP production. When a higher concentration of cholera toxin (300 ng/mL) was used, however, cAMP levels doubled by 2 hr. Despite a lack of responsiveness to purified of SH or oLH, the cells were capable of progesterone and estradiol production when provided with the appropriate substrates. We conclude that PGC-2 display properties that are similar to immature granulosa cells and may provide a suitable in vitro model for the study of granulosa cell function.
Mol Reprod Dev 1996 Nov
PMID:Steroidogenic properties of a spontaneously established porcine granulosa cell line (PGC-2). 891 40

During the early stages of development various cell adhesion molecules (CAMs) and fibroblast growth factor receptors (FGFR) are expressed throughout the retinal neuroepithelium. The ability of retinal ganglion cells to project their axons to the optic fissure depends, in part, on cell-cell interactions mediated by cell adhesion molecules. In the present study we show that the ability of the firstborn rat retinal ganglion cells to extend axons in vitro can be stimulated by NCAM and L1, but not N-cadherin. Both CAM responses can be fully inhibited by antibodies that block neuronal fibroblast growth factor receptor function and by agents that block defined steps in the FGFR signal transduction cascade. When added to living E13.5 rat retinal whole-mount preparations the same agents induced errors in the orderly establishment of young axon patterns in the retinal periphery and caused axons in the retinal center to defasciculate. These results suggest that the activation of the fibroblast growth factor receptor signal cascade not only promotes survival and proliferation of various cell types but can also mediate intraretinal axon guidance.
Mol Cell Neurosci 1996
PMID:Fibroblast growth factor receptor function is required for the orderly projection of ganglion cell axons in the developing mammalian retina. 891 29

During the early stages of development various cell adhesion molecules (CAMs) and fibroblast growth factor receptors (FGFR) are expressed throughout the retinal neuroepithelium. The ability of retinal ganglion cells to project their axons to the optic fissure depends, in part, on cell-cell interactions mediated by cell adhesion molecules. In the present study we show that the ability of the firstborn rat retinal ganglion cells to extend axons in vitro can be stimulated by NCAM and L1, but not N-cadherin. Both CAM responses can be fully inhibited by antibodies that block neuronal fibroblast growth factor receptor function and by agents that block defined steps in the FGFR signal transduction cascade. When added to living E13.5 rat retinal whole-mount preparations the same agents induced errors in the orderly establishment of young axon patterns in the retinal periphery and caused axons in the retinal center to defasciculate. These results suggest that the activation of the fibroblast growth factor receptor signal cascade not only promotes survival and proliferation of various cell types but can also mediate intraretinal axon guidance.
Mol Cell Neurosci 1996 Aug
PMID:Fibroblast Growth Factor Receptor Function Is Required for the Orderly Projection of Ganglion Cell Axons in the Developing Mammalian Retina 895 27

Previously, our laboratory purified and isolated the cDNA for OBCAM (opioid binding cell adhesion molecule) from bovine brain, as well as highly homologous rat brain cDNA clones, SG13 and DUZ-1. Structural similarities with members of the immunoglobulin superfamily suggest a possible role for OBCAM in cell adhesion and recognition, while studies in our own laboratory suggest that OBCAM is important in the regulation of opioid binding and signal transduction. However, OBCAM lacks a putative transmembrane domain, and its possible mode of linkage to the cellular membrane has not been studied. Upon transfection of Cos 1 cells with SG13 and DUZ-1 cDNAs, the OBCAM-homologous proteins were expressed on the surface of the Cos 1 cells. These proteins were released from the membrane of the Cos 1 cells upon digestion with phosphatidylinositol-specific phospholipase C (PI-PLC), demonstrating that they are linked to the membrane via a phosphatidylinositol (PI) linkage. These results are consistent with a role for OBCAM in cell recognition and adhesion, as well as in cellular signaling.
Brain Res Mol Brain Res 1996 Mar
PMID:Expression of OBCAM-related cDNA clones in Cos 1 cells: evidence for a phosphatidylinositol linkage to the cell membrane. 896 53

We have previously reported a 50 kDa glycoprotein (AvGp50) expressed specifically in the chick nervous system [Hancox, K.A., Sheppard, A.M. and Jeffrey, P.L., Characterisation of a novel glycoprotein (AVGP50) in the avian nervous system, with a monoclonal antibody, Dev. Brain Res., 70 (1992) 25-37], and we present its molecular characterization. A PCR fragment was generated following sequencing of peptide and N-terminal fragments derived from purified AvGp50. A 1.58 kb clone (pUEX762) containing the 5'-UTR, the entire coding sequence and a short 3'-UTR was then isolated from a chick embryonic day 18 forebrain library. The deduced amino acid sequence encodes a 338 amino acid peptide containing a 31 amino acid signal peptide at the N-terminal and a 19 amino acid phosphatidylinositol glycan linkage sequence at the C-terminal. The mature protein contains three C2-immunoglobulin-like domains and a glycosyl phosphatidylinositol anchor and shares significant homology to other members of the immunoglobulin superfamily, including neural cell adhesion molecule (N-CAM), myelin-associated glycoprotein (MAG) and the Drosophila protein Amalgam. AvGp50 exhibits highest sequence identity to a recently classified subgroup of the immunoglobulin superfamily (IgLONs - immunoglobulin LAMP, OBCAM and neurotrimin - classified by Pimenta et al. [Pimenta, A.F., Zhukareva, V., Barbe, M.F., Reinoso, B.S., Grimley, C., Henzel, W., Fischer, I. and Levitt, P., The limbic system-associated membrane protein is an Ig superfamily member that mediates selective neuronal growth and axon targeting, Neuron, 15 (1995) 287-297], comprising the opioid binding cell adhesion molecule (OBCAM), neurotrimin and the limbic system-associated membrane protein (LAMP) suggesting that AvGp50 is a member of this subgroup. AvGp50 is expressed predominantly on the cell surface of axons, in particular Purkinje cell and granule cell axons in the cerebellum. In cerebellar and forebrain neuronal cultures, protein expression is exclusively located at the cell surface. Despite its cell surface localization, AvGp50 does not directly influence the outgrowth of neurons from explant cultures from ED8 to ED10 chick forebrain, prompting the suggestion that AvGp50 may act in later maturational events.
Brain Res Mol Brain Res 1997 Mar
PMID:AvGp50, a predominantly axonally expressed glycoprotein, is a member of the IgLON's subfamily of cell adhesion molecules (CAMs). 907 69

The neural cell adhesion molecule (NCAM), probably the best characterized and most abundant cell adhesion molecule on neurons, is thought to be a major regulator of axonal growth and pathfinding. Here we present a detailed analysis of these processes in mice deficient for all NCAM isoforms, generated by gene targeting. The hippocampal mossy fiber tract shows prominent expression of polysialylated NCAM and the generation of new axonal projections throughout life. Focusing on this important intrahippocampal connection, we demonstrate that in the absence of NCAM, fasciculation and pathfinding of these axons are strongly affected. In addition we show alterations in the distribution of mossy fiber terminals. The phenotype is more severe in adult than in young animals, suggesting an essential role for NCAM in the maintenance of plasticity in the mature nervous system.
Mol Cell Neurosci 1997
PMID:NCAM is essential for axonal growth and fasciculation in the hippocampus. 907 95

Unlike most other cellular proteins, the chemoattractant receptor, cAR1, of Dictyostelium is resistant to extraction by the zwitterionic detergent, CHAPS. We exploited this property to isolate a subcellular fraction highly enriched in cAR1 by flotation of CHAPS lysates of cells in sucrose density gradients. Immunogold electron microscopy studies revealed a homogeneous preparation of membrane bilayer sheets. This preparation, designated CHAPS-insoluble floating fraction (CHIEF), also contained a defined set of 20 other proteins and a single uncharged lipid. Cell surface biotinylation and preembedding immunoelectron microscopy both confirmed the plasma membrane origin of this preparation. The cell surface phosphodiesterase (PDE) and a downstream effector of cAR1, adenylate cyclase (ACA), were specifically localized in these structures, whereas the cell adhesion molecule gp80, most of the major cell surface membrane proteins, cytoskeletal components, the actin-binding integral membrane protein ponticulin, and G-protein alpha- and beta-subunits were absent. Overall, CHIFF represents about 3-5% of cell externally exposed membrane proteins. All of these results indicate that CHIFF is derived from specialized microdomains of the plasma membrane. The method of isolation is analogous to that of caveolae. However, we were unable to detect distinct caveolae-like structures on the cell surface associated with cAR1, which showed a diffuse staining profile. The discovery of CHIFF facilitates the purification of cAR1 and related signaling proteins and the biochemical characterization of receptor-mediated processes such as G-protein activation and desensitization. It also has important implications for the "fluid mosaic" model of the plasma membrane structures.
Mol Biol Cell 1997 May
PMID:Identification of detergent-resistant plasma membrane microdomains in dictyostelium: enrichment of signal transduction proteins. 916 71

Functional recovery from peripheral nerve injury and repair depends on a multitude of factors, both intrinsic and extrinsic to neurons. Neuronal survival after axotomy is a prerequisite for regeneration and is facilitated by an array of trophic factors from multiple sources, including neurotrophins, neuropoietic cytokines, insulin-like growth factors (IGFs), and glial-cell-line-derived neurotrophic factors (GDNFs). Axotomized neurons must switch from a transmitting mode to a growth mode and express growth-associated proteins, such as GAP-43, tubulin, and actin, as well as an array of novel neuropeptides and cytokines, all of which have the potential to promote axonal regeneration. Axonal sprouts must reach the distal nerve stump at a time when its growth support is optimal. Schwann cells in the distal stump undergo proliferation and phenotypical changes to prepare the local environment to be favorable for axonal regeneration. Schwann cells play an indispensable role in promoting regeneration by increasing their synthesis of surface cell adhesion molecules (CAMs), such as N-CAM, Ng-CAM/L1, N-cadherin, and L2/HNK-1, by elaborating basement membrane that contains many extracellular matrix proteins, such as laminin, fibronectin, and tenascin, and by producing many neurotrophic factors and their receptors. However, the growth support provided by the distal nerve stump and the capacity of the axotomized neurons to regenerate axons may not be sustained indefinitely. Axonal regenerations may be facilitated by new strategies that enhance the growth potential of neurons and optimize the growth support of the distal nerve stump in combination with prompt nerve repair.
Mol Neurobiol
PMID:The cellular and molecular basis of peripheral nerve regeneration. 917 Jan 1

E587 antigen, an L1-related cell adhesion molecule, is expressed by growing axons and has previously been shown to enhance axon growth and to mediate fasciculation of axons from newborn retinal ganglion cells in goldfish. In zebrafish, the monoclonal antibody E17 against E587 antigen stains all axons in the primary tracts and commissures from 17 h postfertilization (pf) onward and axons which are added subsequently to this scaffold. Moreover, Fab fragments of an E587 antiserum (E587 Fabs) injected into the ventricle of 30-h pf zebrafish embryos caused a marked defasciculation of distinct axon bundles in the posterior commissure, in hindbrain commissures, and in longitudinal tracts of the hindbrain, where they also caused increased crossings between fascicles. The regulated expression of E587 antigen by all developing axons and the effects caused by E587 Fabs show that E587 antigen contributes to the formation of tight and orderly fascicles in the developing CNS.
Mol Cell Neurosci 1997 Jan
PMID:Expression of an L1-related cell adhesion molecule on developing CNS fiber tracts in zebrafish and its functional contribution to axon fasciculation. 920 81


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