Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the effects of substrate-bound laminin on levels of enzymes of the catecholamine biosynthetic pathway in primary cultures of calf adrenal chromaffin cells. Laminin increases the levels of the enzymes tyrosine hydroxylase, dopamine-beta-hydroxylase, and phenylethanolamine-N-methyl-transferase. This effect is selective, in that levels of other enzymes (lactate dehydrogenase, aromatic amino acid decarboxylase, and acetylcholinesterase) are not increased. The effect of laminin can be blocked by antibodies directed against a fragment of the heparin-binding domain of the molecule, whereas antibodies directed against other fragments do not block the increase in tyrosine hydroxylase. Thus the laminin domain involved in enzyme regulation in chromaffin cells is apparently the same as that previously implicated in laminin's interactions with neurons to potentiate survival and stimulate neurite outgrowth (Edgar, D., R. Timpl, and H. Thoenen, 1984, EMBO (Eur. Mol. Biol. Organ.) J., 3:1463-1468). The increase in chromaffin cell tyrosine hydroxylase levels is preceded by an activation of the enzyme in which the Vmax (but not the Km) is altered. The effects of laminin appear to be developmentally regulated, since neither activation nor increased levels of tyrosine hydroxylase occur in adult adrenal chromaffin cells exposed to laminin.
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PMID:Laminin increases both levels and activity of tyrosine hydroxylase in calf adrenal chromaffin cells. 286 97

A combination of direct fluorescence and indirect immunofluorescence microscopy has been used to compare the distribution of the acetylcholine receptor with the distribution of major cytoskeletal and extracellular matrix components during electrocyte differentiation in the electric organs of Torpedo marmorata. Laminin, fibronectin and extracellular matrix proteoglycan are always more extensively distributed around the differentiating cell than the acetylcholine receptor-rich patch that forms on the ventral surface of the cell. The distribution of acetylcholinesterase within the ventral surface of the differentiating electrocyte closely resembles the distribution of the acetylcholine receptor. Areas of apparently high acetylcholine receptor density within the ventrally forming acetylcholine receptor-rich patch are always areas of apparently high extracellular matrix proteoglycan density but are not always areas of high laminin or fibronectin density. Desmin levels appear to increase at the onset of differentiation and desmin initially accumulates in the ventral pole of each myotube as it begins to form an electrocyte. During differentiation F-actin-positive filament bundles are observed that extend from the nuclei down to the ventrally forming acetylcholine receptor-rich patch. Most filament bundles terminate in the acetylcholine receptor-rich region of the cell membrane. Electron-microscopic autoradiography suggests that the filament bundles attach to the membrane at sites where small acetylcholine receptor clusters are found. The results of this study suggest that, out of the four extracellular matrix components studied, only the distribution of acetylcholinesterase (which may be both matrix- and membrane-bound at this stage) closely parallels that of the acetylcholine receptor, and that F-actin filament bundles terminate in a region of the cell that is becoming an area of high acetylcholine receptor density.
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PMID:Development of the electromotor system of Torpedo marmorata: distribution of extracellular matrix and cytoskeletal components during acetylcholine receptor focalization. 356 8

We have studied the influence of the extracellular matrix (ECM) on the amount of beta-amyloid precursor protein (APP) and C-terminal amyloid-bearing fragments in 313 fibroblasts. After incubation with ECM components, the cellular APP content of 3T3 cells changed. Besides, different substrata including collagen, fibronectin, laminin, vitronectin, and heparin, determined changes in the amount of a C-terminal 22 kDa-fragment. The regulation of amyloidogenic fragments by the ECM was transient; in fact, when 3T3 cells were plated on tissue culture dishes coated with collagen or vitronectin, maximal levels of the 22 kDa fragment were observed 12 h after plating; in the presence of fibronectin, the maximum level of the amyloidogenic fragment was obtained 36 h after plating. These results indicate that the ECM modulates in a transient way the generation of APP-derived polypeptides containing the amyloid-beta-peptide (A beta). The ECM does not have a generalized effect on 3T3 fibroblasts, because no significant differences in cell attachment, growth rate, whole-cell polypeptide pattern beta 1 integrin and alpha-tubulin levels were observed on cells grown on various matrix proteins. Laminin, collagen, and heparin also influence the level of an amyloidogenic fragment of 35 kDa in Neuro 2A neuronal cells, without a significant change in the neuronal marker acetylcholinesterase. In this case, however, a long-lasting response to ECM molecules was observed. These observations provide evidence that ECM molecules influence APP biogenesis, including the generation of amyloidogenic fragments containing the A beta peptide. Our studies might prove significant to understand the localized increment of beta-amyloid deposition in selected areas of the brain of Alzheimer's patients.
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PMID:Extracellular matrix regulates the amount of the beta-amyloid precursor protein and its amyloidogenic fragments. 859 96

Acetylcholinesterase (EC 3.1.1.7; AChE) is known to induce neurite outgrowth and differentiation, but its ligands are as yet unknown. Laminin-1 and collagen IV were investigated as potential ligands for AChE. We observed specific saturable binding of biotinylated human AChE to mouse laminin and human collagen, with K(d) values of 4.9482 nM (SE 0.3145 nM) and 1.1617 nM (SE 0.1921 nM) respectively. Peripheral anionic site inhibitors (fasciculin, BW284c51, propidium and gallamine) also significantly reduced binding with fasciculin being the most effective. Significant reductions in AChE-laminin and AChE-collagen interactions were produced by a monoclonal anti-AChE antibody known to react with the peripheral anionic site, and a partial reduction with an antibody that partially recognises the site. Self-association of AChE was also observed (K(d)=16.3235 nM; SE 5.8120 nM); increasing markedly at low pH, but not significantly affected by either inhibitors or antibodies, suggesting a non-specific aggregation phenomenon. Binding to laminin and collagen was significantly reduced by increasing ionic strength and decreasing pH, indicating a dominant role for electrostatic interactions, and suggesting that the site may be different from the hydrophobic site identified for the AChE-amyloid interaction.
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PMID:Human acetylcholinesterase binds to mouse laminin-1 and human collagen IV by an electrostatic mechanism at the peripheral anionic site. 1252 66

The cell adhesion and neurite outgrowth-promoting function of acetylcholinesterase has been localised to the area of the peripheral anionic site. In order to precisely determine the site involved, we used synthetic peptides representing sequences of the peripheral anionic site and its surrounds, and investigated their binding to a panel of monoclonal antibodies that inhibit cell adhesion/neurite outgrowth and/or to recognise the peripheral anionic site. Binding to laminin-1 and collagen IV was also investigated. A relationship between recognition of the sequence 37-50, representing a surface loop adjacent to the peripheral anionic site, and the degree of inhibition of cell adhesion was observed; both laminin-1 and collagen IV also bound this loop with high affinity. Neurite outgrowth on coverslips coated with this peptide was similar to those coated with acetylcholinesterase itself. Adhesion-inhibiting antibodies also recognised the omega loop 69-96, as did laminin-1 and collagen IV. Laminin also bound the sequences 55-66 and 340-353, recognised by the antibodies to varying degrees, but collagen did not. All these peptides were able to promote neurite outgrowth to some degree. No binding to the amyloid-binding omega loop 275-304 by the ligands was observed, nor did the antibodies recognise this consistently. No relationship was observed between the degree of inhibition of acetylcholinesterase and inhibition of neurite outgrowth by the antibodies from which we conclude that the neurite outgrowth function is non-cholinergic. In conclusion, we have identified a specific conformational structure on acetylcholinesterase, comprising adjacent surface loops between residues 37-50 and 69-96, with additional involvement of the sequences 55-66 and 340-353, that mediates cell adhesion and neurite outgrowth.
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PMID:Identification of a structural site on acetylcholinesterase that promotes neurite outgrowth and binds laminin-1 and collagen IV. 1517 27