Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The possible role of neural cell adhesion molecule (NCAM) in myelination was studied in the dysmyelinating mouse mutants jimpy and shiverer, by characterizing the expression of the different molecular forms of brain NCAM as a function of age. In jimpy, the expression of NCAM-120 (120,000-Da NCAM) was low and in shiverer both NCAM-120 and NCAM-180 (180,000-Da NCAM) were reduced when compared to controls. In both jimpy and shiverer there was no significant change in the phospholipase C-sensitive NCAM-120. These data further support the possibility that NCAM may be involved in myelination.
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PMID:Expression of neural cell adhesion molecule in dysmyelinating mutants. 229 27

Primitive clonogenic progenitor cells in human bone marrow bind to preformed marrow-derived stromal layers in vitro and generate colonies of blast cells. The binding interaction does not require calcium or magnesium ions and occurs equally well in serum-free and serum-supplemented culture medium. It does not appear to involve known cell adhesion molecules (CAMs) for which monoclonal antibodies are available (integrins, N-CAM, LFA-1, and ICAM-1), and we were unable to demonstrate a role for the progenitor cell antigen CD34 in progenitor cell adhesion to cultured stroma. The CAM expressed by the blast colony-forming cells may exist in transmembrane or phosphatidylinositol (PI)-linked forms because it is only partially degraded by exposure to trypsin or to PI-specific phospholipase C. However, binding of these cells to stroma is not prevented in the presence of monoclonal antibodies reacting with known PI-linked structures (Thy-1, CD14, and CD16). It is either masked by neuraminidase-sensitive residues or is no longer expressed as cells mature, respectively, along the granulocytic or erythroid lineages. The properties of the hemopoietic progenitor CAM are discussed with reference to the properties of other CAMs and of hemopoietic progenitor cell markers.
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PMID:Hemopoietic progenitor cell binding to the stromal microenvironment in vitro. 237 49

During myogenesis myoblasts fuse to form multinucleate cells that express muscle-specific proteins. A specific cell-cell adhesion process precedes lipid bilayer union during myoblast fusion (Knudsen, K. A., and A. F. Horwitz. 1977. Dev. Biol. 58:328-338) and is mediated by cell surface glycoproteins (Knudsen, K. A., 1985. J. Cell Biol. 101:891-897). In this paper we show that myoblast adhesion and myotube formation are inhibited by treating fusion-competent myoblasts with phosphatidylinositol-specific phospholipase C (PI-PLC). The effect of PI-PLC on myoblast adhesion is dose dependent and inhibited by D-myo-inositol 1-monophosphate and the effect on myotube formation is reversible, suggesting a specific, nontoxic effect on myogenesis by the enzyme. A soluble form of adhesion-related glycoproteins is released from fusion-competent myoblasts by treatment with PI-PLC as evidenced by (a) the ability of phospholipase C (PLC)-released material to block the adhesion-perturbing activity of a polyclonal antiserum to intact myoblasts; and (b) the ability of PLC-released glycoprotein to stimulate adhesion-perturbing antisera when injected into mice. PI-PLC treatment of fusion-competent myoblasts releases an isoform of N-CAM into the supernate, suggesting that N-CAM may participate in mediating myoblast interaction during myogenesis.
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PMID:Involvement of cell surface phosphatidylinositol-anchored glycoproteins in cell-cell adhesion of chick embryo myoblasts. 279 39

In embryonic chicken brains, the neural cell adhesion molecule N-CAM is expressed mainly as two polypeptides, the large intracellular-domain polypeptide (ld) (Mr = 160,000) and the small intracellular-domain polypeptide (sd) (Mr = 130,000) chains, that differ in their cytoplasmic domains and that arise by alternative splicing of RNA transcribed from a single gene. There is evidence for a minor N-CAM polypeptide of Mr = 120,000 that is similar to the ld and sd chains for most of its amino-terminal sequence, but which lacks a cytoplasmic domain. We report here the isolation and characterization of a cDNA clone, lambda N151, that appears to encode this third N-CAM polypeptide, which we designate the ssd (small surface-domain) polypeptide chain. The cDNA insert of lambda N151 consists of 2437 base pairs (bp). DNA hybridization and sequencing indicate that the first 1721 bp are nearly identical to the corresponding sequences of clone lambda N208, which encodes the ld chain. Following in the same reading frame, lambda N151 encodes 25 amino acids not present in lambda N208. The rest of lambda N151 consists of a 637-bp noncoding region containing an AATACA polyadenylylation sequence and a 55-bp poly(A) tract. Messenger RNAs complementary to lambda N151 appear later in development than those complementary to the ld and sd chains, and their appearance is correlated with the appearance of the ssd polypeptide. Although the polypeptide encoded by lambda N151 lacks a membrane region that would define a cytoplasmic domain, it does contain at its carboxyl end a relatively hydrophobic stretch of amino acids similar to those seen in precursors of membrane proteins that are attached to membranes via the lipid phosphatidylinositol. We show here that the ssd chain of chicken N-CAM can be released from brain vesicles by treatment with phospholipase C, suggesting that it too may have a phosphatidylinositol anchor. These results define two additional modes by which N-CAM expression can be modulated: by RNA splicing at a new site and by differential membrane attachment of the resulting polypeptide through a lipid intermediate.
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PMID:cDNA clones of the neural cell adhesion molecule (N-CAM) lacking a membrane-spanning region consistent with evidence for membrane attachment via a phosphatidylinositol intermediate. 346 41

The rodent neural cell adhesion molecule (NCAM) consists of three glycoproteins with Mr of 180,000, 140,000 and 120,000. The Mr 120,000 protein (NCAM-120) has been shown to exist in membrane-bound and soluble forms but the nature of its membrane association and release has remained obscure. We show here that phosphatidylinositol-specific phospholipase C (PI-PLC), but not a phospholipase C of different specificity, releases a substantial proportion of NCAM-120 from brain membranes and solubilizes almost quantitatively NCAM-120 present at the surface of C6 astroglial cells. The PI-PLC effect was highly selective since only one other protein species was detectably released from C6 cells. These results suggest that NCAM-120 is held in the membrane by covalently bound phosphatidylinositol or a closely related lipid in a way similar to several other surface proteins from eukaryotic cells. The presence of NCAM in a form which can be released from the cell surface by a highly selective mechanism raises additional possibilities for modulation and control of cell--cell adhesion.
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PMID:Phosphatidylinositol is involved in the membrane attachment of NCAM-120, the smallest component of the neural cell adhesion molecule. 378 Jun 68

To study the membrane anchoring of the 120 kDa component of the neural cell adhesion molecule N-CAM, the smallest form lacking a transmembrane domain, cultured mouse neural cells were treated with phosphatidylinositol-specific phospholipase C from Staphylococcus aureus. When live cultures of astrocytes and neurons are treated with phosphatidylinositol-specific phospholipase C, N-CAM120 is released into the supernatant. Under these conditions N-CAM140 and N-CAM180 are not released. Phospholipase C from Bacillus cereus or Clostridium perfringens does not release N-CAM120. The embryonic form of N-CAM on astrocytes migrating as a broad band between 120 and 180 kDa is also partially released by phosphatidylinositol-specific phospholipase C as a band migrating between 120 and 160 kDa. These observations suggest novel mechanisms in regulation of N-CAM120 expression on the cell surface and in modulation of N-CAM-mediated cell adhesion.
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PMID:Release of the 120 kDa component of the mouse neural cell adhesion molecule N-CAM from cell surfaces by phosphatidylinositol-specific phospholipase C. 382 37

We have tested the hypothesis that maturation-dependent changes in the cortical plate affect the spatiotemporal growth patterns of developing thalamocortical and corticocortical axonal projections. Given a choice between alternating lanes of embryonic (E18-19) and neonatal (P0-1) rat cortical plate membranes, embryonic (E18-19) thalamic and cortical neurites prefer to extend on neonatal membranes. Thalamic and cortical explants do extend neurites on uniform carpets of E19 cortical plate membranes, but the outgrowth is consistently greater on uniform carpets of P1 cortical plate membranes. These experiments demonstrate a maturation-dependent enhancement in the ability of cortical plate to support neurite growth from thalamic and cortical explants. In contrast, retinal and cerebellar neurites, which do not grow into cortex in vivo, generally grew poorly on these membranes, suggesting a degree of specificity to the neurite growth response. Immunohistochemical analysis of developing cortex suggests that several extracellular matrix (ECM) and cell adhesion molecules are upregulated in cortical plate. However, immunocharacterization of membrane carpets for these same ECM and cell adhesion molecules suggests that the growth preferences of thalamic and cortical neurites in vitro are predominantly influenced by membrane-anchored, rather than ECM, molecules. Western analysis of E19 and P1 cortical plate membranes supports this conclusion, and indicates that the membrane-anchored cell adhesion molecules L1 and N-CAM are more abundant in the P1 cortical plate membrane preparation. Experiments in which cortical plate membranes were treated to remove molecules sensitive to phosphatidylinositol (PI)-specific phospholipase C demonstrate that neurite growth promoters present in E19 cortical plate membranes are predominantly PI linked, whereas those present in P1 membranes are predominantly non-PI linked. These findings indicate that the neurite growth preferences are mediated, at least in part, by an upregulation of neurite growth-promoting molecules in developing cortical plate that are not PI linked. Taken together, these findings suggest that a maturation-dependent upregulation of neurite growth-promoting molecules on cortical plate cells controls the invasion of the cortical plate by thalamocortical and corticocortical axons.
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PMID:Maturation-dependent upregulation of growth-promoting molecules in developing cortical plate controls thalamic and cortical neurite growth. 772 44

A minor fraction of the total ecto-type (E-type) ATPase activity of rat synaptosomes has been detected in immunoprecipitates of the neural cell adhesion molecule, NCAM, indicating that this either is an intrinsic enzymatic activity of NCAM or of an ATPase tightly associated to NCAM [Dzhandzhugazyan & Bock (1993) FEBS Lett. 336, 279-283]. We here demonstrate ATPase activity in preparations of the lipid-anchored as well as the transmembrane NCAM isoforms immunoisolated from transfected L-cells. A fraction of the E-type ATPase activity is spontaneously released from synaptosomes. Released material was fractionated by various chromatographic procedures and an extracellular fragment of NCAM was shown to co-elute with the major part of the enzymatic activity. Furthermore, it was shown that agarose-coupled NCAM-antibodies retained 85% of the ATPase activity released from synaptosomes after treatment with phosphatidylinositol-specific phospholipase C. These findings restricted the association or expression of the enzymatic activity to the extracellular part of NCAM. An affinity reagent, 5'-p-fluorosulfonylbenzoyl adenosine, FSBA, was shown to inhibit ATPase activity of immunoisolated NCAM, and incorporation of FSBA was detected in all three major NCAM isoforms (A, B, and C). An excess of ATP prevented both inactivation of the enzyme and affinity labeling of NCAM. Thus, NCAM contains an ATP-binding site, and this site is localized extracellularly and probably has the catalytic function. Binding of the substrate or FSBA protected a proteolytic cleavage site in NCAM localized close to the membrane presumably by induction of a local conformational change in NCAM, indicating a mechanism by which ATP may regulate NCAM adhesion and adhesion-triggered processes. A possible role of this mechanism in synaptic plasticity and memory consolidation is proposed.
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PMID:Demonstration of an extracellular ATP-binding site in NCAM: functional implications of nucleotide binding. 939 68