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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of experimental paradigms have been used to demonstrate that NCAM, N-cadherin, and L1 stimulate axonal growth. The molecular basis of this response has been extensively studied and a range of agents that inhibit neurite outgrowth stimulated by the above CAMs, but not integrins, have now been identified. These studies pointed to the activation of a tyrosine kinase-PLCgamma cascade as being important for the neurite outgrowth responses stimulated by all three CAMs, and this was substantiated by the identification of agents that could activate the cascade and mimic the growth response. In this review we will suggest that the neurite growth response stimulated by these CAMs is mediated by activation of the fibroblast growth factor receptor (FGFR) in neurons and that this results in the recruitment and activation of PLCgamma via interactions of its SH2 domain with the activated receptor. In this context the key events downstream from activation of PLCgamma required for neurite growth appear to be the conversion of diacylglycerol (DAG) to arachidonic acid (AA) via DAG lipase activity, followed by an increased influx of calcium into the neurons. The evolutionary conservation of putative binding motifs between the above CAMs and the FGFR suggests that activation of the FGFR-PLCgamma cascade by the CAMs might involve a direct CAM-FGFR interaction. The identification of the binding motifs also allows for predictions to be made concerning whether other CAMs might directly interact with the FGFR.
Mol Cell Neurosci 1996 Aug
PMID:CAM-FGF Receptor Interactions: A Model for Axonal Growth 895 25

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

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

Progenitor cells in the mammalian forebrain can undergo either symmetric or asymmetric cell divisions by varying their cleavage orientation. In asymmetric divisions, cells distribute apically and basally localized proteins differentially to their daughters. Here we explore the intrinsic polarity of neuroepithelial cells in the developing telencephalon. Actin microfilaments are concentrated apically, forming beltlike structures that encircle spots of gamma-tubulin immunoreactivity. Staining for N-cadherin, beta-catenin, and the tyrosine kinase substrates pp120 and paxillin is also enriched at the lumenal surface, presumably due to the localization of these proteins at adherens junctions. Phosphotyrosine immunoreactivity is concentrated apically in rings, suggesting that adherens junctions are enriched for signaling molecules. In mitotic cells it appears that adherens junction proteins and phosphotyrosine immunoreactivity may be inherited either symmetrically or asymmetrically, depending on the cell's cleavage orientation during mitosis. The differential inheritance of junctional proteins may determine whether a daughter cell can respond to extrinsic signals after mitosis.
Mol Cell Neurosci 1998 Jul
PMID:Intrinsic polarity of mammalian neuroepithelial cells. 967 50

Cell-cell interactions, mediated by members of the cadherin family of Ca2+-dependent adhesion molecules, play key roles in morphogenetic processes as well as in the transduction of long-range growth and differentiation signals. In muscle differentiation cell adhesion is involved in both early stages of myogenic induction and in later stages of myoblast interaction and fusion. In this study we have explored the involvement of a specific cadherin, namely N-cadherin, in myogenic differentiation. For that purpose we have treated different established lines of cultured myoblasts with beads coated with N-cadherin-specific ligands, including a recombinant N-cadherin extracellular domain, and anti-N-cadherin antibodies. Immunofluorescent labeling for cadherins and catenins indicated that treatment with the cadherin-reactive beads for several hours enhances the assembly of cell-cell adherens-type junctions. Moreover, immunofluorescence and immunoblotting analyses indicated that treatment with the beads for 12-24 h induces myogenin expression and growth arrest, which are largely independent of cell plating density. Upon longer incubation with the beads (2-3 d) a major facilitation in the expression of several muscle-specific sarcomeric proteins and in cell fusion into myotubes was observed. These results suggest that surface clustering or immobilization of N-cadherin can directly trigger signaling events, which promote the activation of a myogenic differentiation program.
Mol Biol Cell 1998 Nov
PMID:Direct involvement of N-cadherin-mediated signaling in muscle differentiation. 980 1

Cadherins form a large family of homophilic cell adhesion molecules that are involved in numerous aspects of neural development. The best-studied neural cadherin, N-cadherin, is concentrated at synapses made by retinal axons in the chick optic tectum and is required for the arborization of retinal axons in their target (retinorecipient) laminae. By analogy, other cadherins might mediate arborization or synaptogenesis in other tectal laminae. Here we consider which cadherins are expressed in tectum, which cells express them, and how their expression is regulated. First, using N-cadherin as a model, we show that synaptic input regulates both cadherin gene expression and the subcellular distribution of cadherin protein. Second, we demonstrate that N-, R-, and T-cadherin are each expressed in distinct laminar patterns during retinotectal synaptogenesis and that N- and R- are enriched in nonoverlapping synaptic subsets. Third, we show that over 20 cadherin superfamily genes are expressed in the tectum during the time that synapses are forming and that many of them are expressed in restricted groups of cells. Finally, we report that both beta-catenin and gamma-catenin (plakoglobin), cytoplasmic proteins required for cadherin signaling, are enriched at synapses and associated with N-cadherin. However, beta- and gamma-catenins are differentially distributed and regulated, and form mutually exclusive complexes. This result suggests that cadherin-based specificity involves multiple cadherin-dependent signaling pathways as well as multiple cadherins.
Mol Cell Neurosci 1998 Nov
PMID:Expression of multiple cadherins and catenins in the chick optic tectum. 982 89

The intercalated disc is an extremely important specialised structure of cardiac muscle. Intercalated disc alterations have been implicated in ischemic and dilated cardiomyopathy. With a chronic aortic stenosis guinea pig model, we demonstrated in the current study substantial intercalated disc remodeling during the progression of compensated left ventricular (LV) hypertrophy to congestive left heart failure. For the first time, we reported that although the abundance of beta-catenin and vinculin remained unchanged as shown by quantitative Western blotting, the normal distribution of beta-catenin and vinculin at intercalated disc sites was relocated into the cell body in a large fraction of LV myocytes. gamma-Catenin did not show a compensatory up-regulation at the intercalated disc sites where beta-catenin concentration was reduced. Both abundance and distribution of the transmembrane protein N-cadherin remained unchanged in this model. While co-labeled N-cadherin remained unchanged, quantitative confocal microscopy shows that the amount of connexin43 per LV myocyte decreased by 37% at the congestive heart failure stage but not at the compensated hypertrophy stage. No compensatory upregulation of connexin45 was evident when connexin43 was decreased in failing LV myocytes. The relocation of beta-catenin and vinculin away from intercalated discs in failing myocytes may impair the mechanical linkage between N-cadherin and thin filaments and adversely affect myocyte shape. Loss of connexin43 in LV myocytes may impair electrical coupling of adjacent myocytes.
J Mol Cell Cardiol 1999 Feb
PMID:Chronic pressure overload cardiac hypertrophy and failure in guinea pigs: III. Intercalated disc remodeling. 1009 46

Several distinct classes of proteins positively regulate axonal growth; some of these are known to activate the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling cascade, at least in nonneuronal cells. We have found that N-cadherin, as well as laminin (LN) and basic fibroblast growth factor (bFGF), can activate ERK in embryonic chick retinal neurons. Additionally, adhesion of retinal neurons to LN or N-cadherin substrates induced a redistribution of ERK from the cytoplasm toward the plasma membrane. Neurite outgrowth induced by bFGF, LN, or N-cadherin was strongly inhibited by treatment with inhibitors of ERK kinase activation, but not by an inhibitor of p38 MAPK. We conclude (1) that N-cadherin and LN can activate ERK in retinal neurons and (2) that activation of ERK is required for full neurite outgrowth induced by these proteins. Our results suggest that ERK activation is one point of convergence for signaling pathways generated by a variety of axon growth inducers.
Mol Cell Neurosci 1999 May
PMID:Distinct neurite outgrowth signaling pathways converge on ERK activation. 1035 98

Astrocytes exclude Schwann cells (SCs) from the central nervous system (CNS) at peripheral nerve entry zones and restrict their migration after transplantation into the CNS. We have modeled the interactions between SCs, astrocytes, and fibroblasts in vitro. Astrocytes and SCs in vitro form separate territories, with sharp boundaries between them. SCs migrate poorly when placed on astrocyte monolayers, but migrate well on various other surfaces such as laminin (LN) and skin fibroblasts. Interactions between individual SCs and astrocytes result in long-lasting adhesive contacts during which the SC is unable to migrate away from the astrocyte. In contrast, SC interactions with fibroblasts are much shorter with less arrest of migration. SCs adhere strongly to astrocytes and other SCs, but less well to substrates that promote migration, such as LN and fibroblasts. SC-astrocyte and SC-SC adhesion is mediated by the calcium-dependent cell adhesion molecule N-cadherin. Inhibition of N-cadherin function by calcium withdrawal, peptides containing the classical cadherin cell adhesion recognition sequence His-Ala-Val, or antibodies directed against this sequence inhibit SC adhesion and increase SC migration on astrocytes. We suggest that N-cadherin-mediated adhesion to astrocytes inhibits the widespread migration of SCs in CNS tissue.
Mol Cell Neurosci 1999 Jul
PMID:N-Cadherin inhibits Schwann cell migration on astrocytes. 1043 18

In MDCK cells, presenilin-1 (PS1) accumulates at intercellular contacts where it colocalizes with components of the cadherin-based adherens junctions. PS1 fragments form complexes with E-cadherin, beta-catenin, and alpha-catenin, all components of adherens junctions. In confluent MDCK cells, PS1 forms complexes with cell surface E-cadherin; disruption of Ca(2+)-dependent cell-cell contacts reduces surface PS1 and the levels of PS1-E-cadherin complexes. PS1 overexpression in human kidney cells enhances cell-cell adhesion. Together, these data show that PS1 incorporates into the cadherin/catenin adhesion system and regulates cell-cell adhesion. PS1 concentrates at intercellular contacts in epithelial tissue; in brain, it forms complexes with both E- and N-cadherin and concentrates at synaptic adhesions. That PS1 is a constituent of the cadherin/catenin complex makes that complex a potential target for PS1 FAD mutations.
Mol Cell 1999 Dec
PMID:Presenilin-1 forms complexes with the cadherin/catenin cell-cell adhesion system and is recruited to intercellular and synaptic contacts. 1063 15


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