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At least 217 records · Page 12Linked to original sources
PubMed1991

Beta amyloid precursor protein mediates neuronal cell-cell and cell-surface adhesion.

The beta-amyloid precursor protein (APP) is a membrane-bound glycoprotein which has been proposed to play a role both as a growth factor and a mediator of cell adhesion. Using the Neuro-2A neuroblastoma cell line, we have investigated the capacity of APP to mediate neural cell adhesion. The cells express the protein at a high level, the immunohistochemical staining pattern at the level of the membrane having a punctate pattern. Fab' fragments of antibodies to the extracellular portion of the molecule were found to inhibit cell binding to a collagen substrate, but not to laminin, fibronectin, or poly-l-lysine. Fab' fragments of antibodies to the nerve cell adhesion molecule N-CAM also inhibited binding of Neuro-2A cells specifically to collagen. This inhibition of cell-surface binding was accompanied by a repression of neurite outgrowth in differentiating cells in the presence of antibodies. APP antibodies also inhibited neuron-neuron and neuron-glial binding, but not glial-glial cell adhesion. These data suggest that the APP, which is expressed primarily on differentiated neuronal cells, may play a role in the mediation of both cell-cell and cell-substrate adhesion.

Amyloid beta-Peptides↗
PubMed2004

Contactin associates with sodium channel Nav1.3 in native tissues and increases channel density at the cell surface.

The upregulation of voltage-gated sodium channel Na(v)1.3 has been linked to hyperexcitability of axotomized dorsal root ganglion (DRG) neurons, which underlies neuropathic pain. However, factors that regulate delivery of Na(v)1.3 to the cell surface are not known. Contactin/F3, a cell adhesion molecule, has been shown to interact with and enhance surface expression of sodium channels Na(v)1.2 and Na(v)1.9. In this study we show that contactin coimmunoprecipitates with Na(v)1.3 from postnatal day 0 rat brain where this channel is abundant, and from human embryonic kidney (HEK) 293 cells stably transfected with Na(v)1.3 (HEK-Na(v)1.3). Purified GST fusion proteins of the N and C termini of Na(v)1.3 pull down contactin from lysates of transfected HEK 293 cells. Transfection of HEK-Na(v)1.3 cells with contactin increases the amplitude of the current threefold without changing the biophysical properties of the channel. Enzymatic removal of contactin from the cell surface of cotransfected cells does not reduce the elevated levels of the Na(v)1.3 current. Finally, we show that, similar to Na(v)1.3, contactin is upregulated in axotomized DRG neurons and accumulates within the neuroma of transected sciatic nerve. We propose that the upregulation of contactin and its colocalization with Na(v)1.3 in axotomized DRG neurons may contribute to the hyper-excitablity of the injured neurons.

Animals↗
PubMed1997

L1-associated diseases: clinical geneticists divide, molecular geneticists unite.

The neuronal cell adhesion molecule L1 (L1CAM) is a transmembrane glycoprotein belonging to the immunoglobulin superfamily and is essential in the development of the nervous system. It is mainly expressed on neurons and Schwann cells, and plays a key role in axon outgrowth and pathfinding through interactions with various extracellular ligands and intracellular second messenger systems. Mutations in L1 are responsible for a wide spectrum of neurologic abnormalities and mental retardation. This spectrum includes X-linked hydrocephalus, MASA syndrome, X-linked complicated spastic paraplegia type 1 and X-linked agenesis of the corpus callosum. These four diseases were initially described as distinct clinical entities with an overlapping clinical spectrum, but can now be lumped into one syndrome caused by mutations in the L1 gene. The main clinical features of this spectrum are Corpus callosum hypoplasia, mental Retardation, Adducted thumbs, Spastic paraplegia and Hydrocephalus, which has led to the acronym CRASH syndrome.

Agenesis of Corpus Callosum↗
PubMed1995

Molecular genetics of neuronal adhesion.

Cell-cell and cell-matrix interactions are believed to play crucial roles in neural development. Cell adhesion molecules of the immunoglobulin and cadherin families, as well as integrin heterodimers and extracellular matrix glycoproteins, are widely expressed in the nervous system. The advent of gene targeting technology has heralded a new era for study of their function. Initial observations in 'knockout' mice have yielded some surprising results.

Animals↗
PubMed1987

The N-CAM D2-protein as marker for synaptic remodelling in the red nucleus.

We have followed the time-course of changes in the concentration of 3 neuronal and one glial antigen in the red nucleus in rats after unilateral lesion of the cerebellorubral connections. The neuronal markers were the neuronal cell adhesion molecule (N-CAM) D2-protein which is prevalent in newly formed neuronal membranes, and the D1- and D3-proteins, which are found mainly in mature neuronal membranes. The glial marker was S-100, a cytoplasmic protein. Six days after the lesion no changes in the concentration of the markers were found in the partially deafferentiated red nucleus. However, 10 days after the lesion the D2-protein concentration was significantly increased, in contrast to the D1-protein concentration which was decreased. After a further 3 days the D2-protein concentration began to decrease, approaching the still significantly decreased D1-protein concentration. Twenty-one days after the lesion the marker protein concentrations were not significantly changed from normal. However, whereas the concentrations of neuronal membrane markers were lower, the glial S-100 concentration showed a tendency to increase. Furthermore, although the changes in D3-protein concentration were unable to reach statistical significance alone they always followed the direction of D1-protein and were significantly in variance with the changes in D2-protein and S-100 concentrations. Our results support the notion of the N-CAM D2-protein as a useful marker for synaptic turnover in adult brain.

Animals↗
PubMed1998

Cis-activation of L1-mediated ankyrin recruitment by TAG-1 homophilic cell adhesion.

Neural cell adhesion molecules (CAMs) of the immunoglobulin (Ig) superfamily mediate not only cell aggregation but also growth cone guidance and neurite outgrowth. In this study we demonstrate that two neural CAMs, L1-CAM and TAG-1, induce the homophilic aggregation of Drosophila S2 cells but are unable to interact with each other when expressed on different cells (trans-interaction). However, immunoprecipitations from cells co-expressing L1-CAM and TAG-1 showed a strong cis-interaction between the two molecules in the plane of the plasma membrane. TAG-1 is linked to the membrane by a glycosylphosphatidylinositol (GPI) anchor and therefore is unable to directly interact with cytoplasmic proteins. In contrast, L1-CAM-mediated homophilic cell adhesion induces the selective recruitment of the membrane skeleton protein ankyrin to areas of cell contact. Immunolabeling experiments in which S2 cells expressing TAG-1 were mixed with cells co-expressing L1-CAM and TAG-1 demonstrated that the homophilic interaction between TAG-1 molecules results in the cis-activation of L1-CAM to bind ankyrin. This TAG-1-dependent recruitment of the membrane skeleton provides an example of how GPI-anchored CAMs are able to transduce signals to the cytoplasm. Furthermore, such interactions might ultimately result in the recruitment and the activation of other signaling molecules at sites of cell contacts.

Animals↗
PubMed1999

Isolation and characterization of mammalian homologues of Caenorhabditis elegans lin-7: localization at cell-cell junctions.

In Caenorhabditis elegans, the vulval induction is mediated by the let-23 receptor tyrosine kinase (RTK)/ Ras signaling pathway. The precise localization of the let-23 RTK at the epithelial junctions is essential for the vulval induction, and requires three genes including lin-2, -7, and -10. The mammalian homologue of lin-2 has been identified as a protein interacting with a neuronal adhesion molecule, neurexin, and named CASK. CASK has recently been reported to interact with syndecans and an actin-binding protein, band 4.1, at epithelial and synaptic junctions, and to play central roles in the formation of cell-cell junctions. The product of C. elegans lin-7 directly interacts with let-23 RTK and localize it at epithelial junctions. Here, we report three rat homologues of lin-7 ubiquitously expressed in various tissues. These homologues are accumulated at the junctional complex region in cultured Madin-Darby canine kidney cells, and are also localized at the synaptic junctions in neurons. The mammalian homologues of lin-7 may be implicated in the formation of cell-cell junctions.

Amino Acid Sequence↗
PubMed1990

Central nervous system antigen P84 can serve as a substrate for neurite outgrowth.

Neurite outgrowth promoting properties of neural cell surface proteins can be assessed by immobilizing isolated membrane proteins on nitrocellulose-coated petri dishes. Using this method, we have identified a unique cell surface antigen, designated P84, as a new neural cell adhesion molecule. Immunoaffinity purified P84 contains three polypeptides with molecular weights of 167, 85, and 66 kDa. When spotted onto nitrocellulose-coated plates, P84 supports adhesion of mouse cerebellar neurons and neurite outgrowth. Glial cell attachment was also observed. Intact monoclonal antibodies directed against P84 inhibit adhesion and outgrowth on a P84 substrate. This antigen is found on the surfaces of neurons in cultures of cerebellar cells. It is also found on a subclass of unidentified flat cells. P84 is not found on oligodendrocytes or GFAP-positive astrocytes. As early as E9, P84 could be detected in the floor plate region of the spinal cord. This pattern persists throughout embryonic development. Postnatally, widespread expression of P84 is observed in a variety of CNS tissues.

Aging↗
PubMed1997

Turnover studies of the neural cell adhesion molecule NCAM: degradation of NCAM in PC12 cells depends on the presence of NGF.

The neural cell adhesion molecule NCAM is a member of the immunoglobulin superfamily and involved in path finding and outgrowth of neurites in vitro. PC12 cells express two major isoforms of NCAM (NCAM180 and NCAM140) and undergo neuronal differentiation, e.g., neurite formation, in response to NGF. Using this cell system, we determined the half-life time of both NCAM isoforms in the absence and presence of NGF. Half-life time of NCAM140 is similar in the presence and absence of NGF, whereas the half-life time of NCAM180 is increased in the presence of NGF. Furthermore, we quantified protein expression of both NCAM isoforms in the presence or absence of NGF and found a decrease of NCAM protein expression in course of neuronal differentiation.

Amino Acid Sequence↗
PubMed2001

Reelin is a serine protease of the extracellular matrix.

Reelin is an extracellular matrix protein that plays a pivotal role in development of the central nervous system. Reelin is also expressed in the adult brain, notably in the cerebral cortex, where it might play a role in synaptic plasticity. The mechanism of action of reelin at the molecular level has been the subject of several hypotheses. Here we show that reelin is a serine protease and that proteolytic activity is relevant to its function, since (i) Reelin expression in HEK 293T cells impairs their ability to adhere to fibronectin-coated surfaces, and adhesion to fibronectin is restored by micromolar concentrations of diisopropyl phosphorofluoridate, a serine hydrolase inhibitor; (ii) purified Reelin binds FP-Peg-biotin, a trap probe which irreversibly binds to serine residues located in active catalytic sites of serine hydrolases; (iii) purified Reelin rapidly degrades fibronectin and laminin, while collagen IV is degraded at a much slower rate; fibronectin degradation is inhibited by inhibitors of serine proteases, and by monoclonal antibody CR-50, an antibody known to block the function of Reelin both in vitro and in vivo. The proteolytic activity of Reelin on adhesion molecules of the extracellular matrix and/or receptors on neurons may explain how Reelin regulates neuronal migration and synaptic plasticity.

Cell Adhesion↗
PubMed1996

L1, N-cadherin, and laminin induce distinct distribution patterns of cytoskeletal elements in growth cones.

Growth cones are highly motile extensions of growing neuronal processes that have a well-characterized cytoskeleton, which is necessary for motility and directed growth. In culture, neurons have been observed to extend processes on a variety of substrates made of cell adhesion molecules (CAMs) or extracellular matrix molecules (ECM molecules). We have previously shown that retinal ganglion cell (RGC) growth cones exhibit characteristic morphologies dependent on the substrate on which they are grown (Payne et al., 1992: Cell Motil. Cytoskel. 21:65-73). Upon contact with a sharp border between two substrates, the growth cones display rapid changes in morphology (Burden-Gulley et al., 1995: J. Neurosci. 15:4370-4381) that may result from extensive restructuring of the cytoskeleton. In the present study, immunocytochemical methods were used to examine the distribution of three cytoskeletal elements in RGC growth cones growing on L1, N-cadherin, or laminin as well as on dishes coated with alternating lanes of these substrates. Distinct distribution patterns of f-actin, microtubules (MTs), and neurofilaments (NFs) were observed in growth cones growing on individual substrates. At border regions between two substrates, growth cones with extensive lamellipodial contact with the second substrate were observed to have f-actin and MT distribution patterns appropriate for the new substrate encountered. Contact via filopodia alone did not evoke this change. Redistribution of NFs was observed only after the majority of the growth cone had crossed onto the second substrate. These results suggest that actin and MTs, but probably not NFs, are directly influenced by CAMs and ECM molecules to produce changes in growth cone morphology. The distribution of two members of the protein tyrosine kinase family, pp60arc and p59fyn, and phosphorylated tyrosine residues was also examined. No differences were observed in the distribution patterns of the kinases and phosphorylated tyrosine residues in growth cones on any of the substrate molecules tested. In addition, the distribution patterns were unchanged in growth cones that contacted and crossed borders between two substrates. These results suggest that redistribution of pp60arc or p59fyn is not required to produce alterations in growth cone morphology induced by contact with L1, N-cadherin or laminin.

Actins↗
PubMed2001

BDNF increases the number of axotomized rat retinal ganglion cells expressing GAP-43, L1, and TAG-1 mRNA--a supportive role for nitric oxide?

The death of neurons and the limited ability to activate growth-associated genes prevent the restoration of lesioned fiber tracts in the adult mammalian CNS. Here, we characterized the effects of the survival-promoting neurotrophin brain-derived neurotrophic factor (BDNF) on mRNA expression of GAP-43, L1, TAG-1, and SC-1 in axotomized and regenerating rat retinal ganglion cells (RGCs). BDNF led to de novo upregulation of TAG-1 mRNA in axotomized RGCs and to a threefold increase in the number of GAP-43 and L1 mRNA-expressing RGCs. SC-1 expression remained unchanged. However, BDNF did not improve long-distance axon regeneration into a peripheral nerve graft. Surprisingly, potentiating BDNF-mediated neuroprotection by simultaneous administration of a spin trap or a NOS inhibitor counteracted the BDNF-induced growth-associated gene expression. This led us to hypothesize that the BDNF effects on GAP-43, L1, and TAG-1 mRNA expression are mediated by a NO-dependent mechanism. In summary, our data support the idea that survival and axon regeneration of lesioned CNS neurons can be regulated independently.

Animals↗
PubMed1991

A novel cell adhesion molecule, G-CAM, found on cultured rat glia.

Using a monoclonal antibody (mAb), designated AMP1, a novel cell adhesion molecule was identified on rat astrocytes and oligodendrocytes. When confluent monolayers of cultured rat astrocytes were labeled with AMP1, the antigen was discretely localized to the cell surface in regions of cell-cell contacts. The antibody did not label embryonic rat cortical neurons plated on monolayers of neonatal astrocytes, indicating that the antigen is neither present on cultured neurons nor does it reorganize on the glial surface under the neurons. On immunoblots of astrocytic or brain proteins, mAb AMP1 recognized a 106 kDa protein. In the present paper, data are presented demonstrating that the AMP1 antigen is a cell adhesion molecule and is distinct from all the known cell adhesion molecules present on astrocytes: N-CAM, N-cadherin, or members of the beta 1 integrin family. We have tentatively termed this molecule 'glial cell adhesion molecule' (G-CAM).

Animals↗
PubMed1996

Different expression of adhesion molecules on stromal cells and endothelial cells of capillary hemangioblastoma.

Cell-cell and cell-matrix interactions are essential for many basic functions, including differentiation and development. In pathological conditions such as inflammation and tumorigenesis adhesive events also play a major role. Cellular adhesion is mediated by specific molecules expressed by both normal and neoplastic tissues. Capillary hemangioblastoma is a tumor of controversial origin, characterized by two major components, vacuolated stromal cells and a capillary network. In order to shed light on the differentiation of the stromal cells and the interactions between the two major components of hemangioblastoma we studied the expression of several adhesion molecules by immunocytochemistry. The endothelium-associated adhesion molecules (ICAM-1, ICAM-2, VCAM-1, PECAM-1 and ELAM-1) were expressed by endothelial cells within the tumors, but not by stromal cells. In contrast, the stromal cells showed strong neuronal cell adhesion molecule (NCAM/CD56) expression, further distinguishing them from endothelial cells. In addition, the stromal cells expressed CD44, which is of interest, as this membrane protein is linked to ezrin, a cytoskeleton-associated protein also expressed by stromal cells. We conclude that the stromal cells and endothelial cells of capillary hemangioblastoma exhibit quite divergent expression patterns of adhesion molecules. The NCAM expression in stromal cells suggests neuroectodermal or mesenchymal differentiation of this tumor. In addition, the NCAM expression could contribute to the sometimes problematic differential diagnosis between capillary hemangioblastoma and metastatic renal cell carcinoma of the central nervous system.

Capillaries↗
PubMed2001

LAD-1, the Caenorhabditis elegans L1CAM homologue, participates in embryonic and gonadal morphogenesis and is a substrate for fibroblast growth factor receptor pathway-dependent phosphotyrosine-based signaling.

This study shows that L1-like adhesion (LAD-1), the sole Caenorhabditis elegans homologue of the L1 family of neuronal adhesion molecules, is required for proper development of the germline and the early embryo and embryonic and gonadal morphogenesis. In addition, the ubiquitously expressed LAD-1, which binds to ankyrin-G, colocalizes with the C. elegans ankyrin, UNC-44, in multiple tissues at sites of cell-cell contact. Finally, we show that LAD-1 is phosphorylated in a fibroblast growth factor receptor (FGFR) pathway-dependent manner on a tyrosine residue in the highly conserved ankyrin-binding motif, FIGQY, which was shown previously to abolish the L1 family of cell adhesion molecule (L1CAM) binding to ankyrin in cultured cells. Immunofluorescence studies revealed that FIGQY-tyrosine-phosphorylated LAD-1 does not colocalize with nonphosphorylated LAD-1 or UNC-44 ankyrin but instead is localized to sites that undergo mechanical stress in polarized epithelia and axon-body wall muscle junctions. These findings suggest a novel ankyrin-independent role for LAD-1 related to FGFR signaling. Taken together, these results indicate that L1CAMs constitute a family of ubiquitous adhesion molecules, which participate in tissue morphogenesis and maintaining tissue integrity in metazoans.

Amino Acid Motifs↗
PubMed1998

Disturbed Purkinje cell migration due to reduced expression of Reelin by X-irradiation in developing rat cerebellum.

The major histogenetic events of the rat cerebellum take place in the early postnatal days. During this period, precursors of microneurons, such as granule cells, form the external granular layer (EGL), extend over the surface of the primordial cerebellum, and actively proliferate. Postmitotic granule cells leave the EOL and migrate to the internal granular layer (IGL). On the other hand, guided by radial glial fibers, immature Purkinje cells migrate from the ventricular zone of the fourth ventricle and settle in the Purkinje cell plate with thickness of several cells. Various cell adhesion molecules are involved in the interaction between the migratory immature Purkinje cells and processes of the radial glia as the basis for contact guidance. The second process is the formation of immature Purkinje cells to the monolayer. This process takes place at the first week after birth of the rat and cell adhesion molecules such as neural cell adhesion molecule (NCAM), fibronectin, tenascin and Reelin are also suggested to play an important role for the cell patterning. When rat fetuses are exposed to X-radiation in the last gestation period, abnormal foliation of the cerebellum develops with ectopic Purkinje cells. The molecular mechanism that contributes to abnormal migration of Purkinje cells and foliar malformation induced by X-irradiation in the cerebellum are not yet clear. This study was undertaken to elucidate the mechanisms of ectopic Purkinje cell formation by examining the expression of cell adhesion molecules.

Animals↗
PubMed1991

Astrocyte-derived TGF-beta 2 and NGF differentially regulate neural recognition molecule expression by cultured astrocytes.

Because of the importance of neural recognition molecules expressed by glial cells to mediate interactions with neurons, growth factors and cytokines known to be functional during morphogenesis and in diseases of the nervous system were studied for their effects on recognition molecule expression by cultured immature and mature astrocytes from several brain regions. In cultures of immature astrocytes, transforming growth factors-beta 1 (TGF-beta 1) and -beta 2 (TGF-beta 2) and nerve growth factor (NGF) increased expression of the neural adhesion molecule L1, leading to a glia-mediated L1-specific increase in neurite outgrowth of dorsal root ganglion neurons on the astrocyte substrate. L1 expression induced by TGF-beta was inhibited by addition of antibodies to NGF, suggesting that TGF-beta influences L1 expression by modulating production of NGF by astrocytes. TGF-beta 1 and -beta 2 decreased expression of N-CAM by immature astrocytes. Since N-CAM expression was not affected by NGF and antibodies to NGF did not abolish the TGF-beta-induced decrease in N-CAM expression, NGF did not appear to be the mediator for regulating expression of N-CAM. Expression of the adhesion molecule on glia (AMOG) was not affected by any factor. NGF and TGF-beta 2 in latent form, but not TGF-beta 1 were found in the culture supernatants. Addition of interferon-gamma (IFN-gamma), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), platelet-derived growth factor (PDGF), or basic fibroblast growth factor (bFGF) to the cultures did not change recognition molecule expression. REcognition molecule expression by mature astrocytes was not found to be modified by any of the factors tested. In view of the observation that levels of L1 and N-CAM expression correlated with the presence of TGF-beta 2 and NGF in the culture supernatants of immature astrocytes, an autocrine regulatory mechanism for recognition molecule expression by these cells is suggested to play a crucial role in regulation of neuron-glia interactions.

Adenosine Triphosphatases↗