Author Report for: Dai ZNo contact information in database for Dai Z
Luo K, Chen J, Li H, Wu D, Du Y, Zhao S, Liu T, Li L, Dai Z and Fu X <3 more author(s)> Luo K, Chen J, Li H, Wu D, Du Y, Zhao S, Liu T, Li L, Dai Z, Li Y, Zhao Y, Tang L, Fu X (- 3) Ref: Bioorg Chem, 138:106596, 2023 : PubMed ESTHER: Luo_2023_Bioorg.Chem_138_106596 PubMedSearch: Luo 2023 Bioorg.Chem 138 106596 PubMedID: 37186997 Abstract Scutellarein hybrids were designed, synthesized and evaluated as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). Compounds 11a-i, containing a 2-hydroxymethyl-3,5,6-trimethylpyrazine fragment at the 7-position of scutellarein, were found to have balanced and effective multi-target potencies against AD. Among them, compound 11e exhibited the most potent inhibition of electric eel and human acetylcholinesterase enzymes with IC(50) values of 6.72 +/- 0.09 and 8.91 +/- 0.08 microM, respectively. In addition, compound 11e displayed not only excellent inhibition of self- and Cu(2+)-induced Abeta(1-42) aggregation (91.85% and 85.62%, respectively) but also induced disassembly of self- and Cu(2+)-induced Abeta fibrils (84.54% and 83.49% disaggregation, respectively). Moreover, 11e significantly reduced tau protein hyperphosphorylation induced by Abeta(25-35), and also exhibited good inhibition of platelet aggregation. A neuroprotective assay demonstrated that pre-treatment of PC12 cells with 11e significantly decreased lactate dehydrogenase levels, increased cell viability, enhanced expression of relevant apoptotic proteins (Bcl-2, Bax and caspase-3) and inhibited RSL3-induced PC12 cell ferroptosis. Furthermore, hCMEC/D3 and hPepT1-MDCK cell line permeability assays indicated that 11e would have optimal blood-brain barrier and intestinal absorption characteristics. In addition, in vivo studies revealed that compound 11e significantly attenuated learning and memory impairment in an AD mice model. Toxicity experiments with the compound did not reveal any safety concerns. Notably, 11e significantly reduced beta-amyloid precursor protein (APP) and beta-site APP cleaving enzyme-1 (BACE-1) protein expression in brain tissue of scopolamine-treated mice. Taken together, these outstanding properties qualified compound 11e as a promising multi-target candidate for AD therapy, worthy of further studies. Title: Design, synthesis and evaluation of novel scutellarin and scutellarein-N,N-bis-substituted carbamate-l-amino acid derivatives as potential multifunctional therapeutics for Alzheimer's disease Wu D, Chen J, Luo K, Li H, Liu T, Li L, Dai Z, Li Y, Zhao Y, Fu X Ref: Bioorg Chem, 122:105760, 2022 : PubMed ESTHER: Wu_2022_Bioorg.Chem_122_105760 PubMedSearch: Wu 2022 Bioorg.Chem 122 105760 PubMedID: 35349945 Abstract In this study, we designed, synthesized and evaluated a series of scutellarin and scutellarein-N,N-bis-substituted carbamate-l-amino acid derivatives as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). Compounds containing scutellarein as the parent nucleus (6a-l) had good inhibitory activity against acetyl cholinesterase (AChE), with compound 6 h exhibiting the most potent inhibition of electric eel AChE and human AChE enzymes with IC(50) values of 6.01 +/- 1.66 and 7.91 +/- 0.49 microM, respectively. In addition, compound 6 h displayed not only excellent inhibition of self- and Cu(2+)-induced Abeta(1-42) aggregation (89.17% and 86.19% inhibition) but also induced disassembly of self- and Cu(2+)-induced Abeta fibrils (84.25% and 78.73% disaggregation). Moreover, a neuroprotective assay demonstrated that pre-treatment of PC12 cells with 6 h significantly decreased lactate dehydrogenase levels, increased cell viability, enhanced expression of relevant apoptotic proteins (Bcl-2, Bax, and caspase-3) and inhibited RSL3 induced PC12 cell ferroptosis. Furthermore, hCMEC/D3 and hPepT1-MDCK cell line permeability assays indicated that 6 h would have optimal blood-brain barrier and intestinal absorption characteristics. The in vivo experimental data suggested that 6 h ameliorated learning and memory impairment in mice by decreasing AChE activity, increasing ACh levels and alleviating pathological damage of hippocampal tissue cells. These multifunctional properties highlight compound 6 h as a promising candidate for development as a multifunctional drug against AD. Title: Dual regulation of adipose triglyceride lipase by pigment epithelium-derived factor: A novel mechanistic insight into progressive obesity Dai Z, Qi W, Li C, Lu J, Mao Y, Yao Y, Li L, Zhang T, Hong H and Cai W <5 more author(s)> Dai Z, Qi W, Li C, Lu J, Mao Y, Yao Y, Li L, Zhang T, Hong H, Li S, Zhou T, Yang Z, Yang X, Gao G, Cai W (- 5) Ref: Mol Cell Endocrinol, 377:123, 2013 : PubMed ESTHER: Dai_2013_Mol.Cell.Endocrinol_377_123 PubMedSearch: Dai 2013 Mol.Cell.Endocrinol 377 123 PubMedID: 23850519 Abstract Both elevated plasma free fatty acids (FFA) and accumulating triglyceride in adipose tissue are observed in the process of obesity and insulin resistance. This contradictory phenomenon and its underlying mechanisms have not been thoroughly elucidated. Recent studies have demonstrated that pigment epithelium-derived factor (PEDF) contributes to elevated plasma FFA and insulin resistance in obese mice via the activation of adipose triglyceride lipase (ATGL). However, we found that PEDF downregulated adipose ATGL protein expression despite of enhancing lipolysis. Plasma PEDF and FFA were increased in associated with a progressive high-fat-diet, and those outcomes were also accompanied by fat accumulation and a reduction in adipose ATGL. Exogenous PEDF injection downregulated adipose ATGL protein expression and elevated plasma FFA, while endogenous PEDF neutralization significantly rescued the adipose ATGL reduction and also reduced plasma FFA in obese mice. PEDF reduced ATGL protein expression in a time- and dose-dependent manner in differentiated 3T3-L1 cells. Small interfering RNA-mediated PEDF knockdown and antibody-mediated PEDF blockage increased endogenous ATGL expression, and PEDF overexpression downregulated ATGL. PEDF resulted in a decreased half-life of ATGL and regulated ATGL degradation via ubiquitin-dependent proteasomal degradation pathway. PEDF stimulated lipolysis via ATGL using ATGL inhibitor bromoenol lactone, and PEDF also downregulated G0/G1 switch gene 2 (G0S2) expression, which is an endogenous inhibitor of ATGL activation. Overall, PEDF attenuated ATGL protein accumulation via proteasome-mediated degradation in adipocytes, and PEDF also promoted lipolysis by activating ATGL. Elevated PEDF may contribute to progressive obesity and insulin resistance via its dual regulation of ATGL. Title: Comparative genomics of citric-acid-producing Aspergillus niger ATCC 1015 versus enzyme-producing CBS 513.88 Andersen MR, Salazar MP, Schaap PJ, van de Vondervoort PJ, Culley D, Thykaer J, Frisvad JC, Nielsen KF, Albang R and Baker SE <37 more author(s)> Andersen MR, Salazar MP, Schaap PJ, van de Vondervoort PJ, Culley D, Thykaer J, Frisvad JC, Nielsen KF, Albang R, Albermann K, Berka RM, Braus GH, Braus-Stromeyer SA, Corrochano LM, Dai Z, van Dijck PW, Hofmann G, Lasure LL, Magnuson JK, Menke H, Meijer M, Meijer SL, Nielsen JB, Nielsen ML, van Ooyen AJ, Pel HJ, Poulsen L, Samson RA, Stam H, Tsang A, van den Brink JM, Atkins A, Aerts A, Shapiro H, Pangilinan J, Salamov A, Lou Y, Lindquist E, Lucas S, Grimwood J, Grigoriev IV, Kubicek CP, Martinez D, van Peij NN, Roubos JA, Nielsen J, Baker SE (- 37) Ref: Genome Res, 21:885, 2011 : PubMed ESTHER: Andersen_2011_Genome.Res_21_885 PubMedSearch: Andersen 2011 Genome.Res 21 885 PubMedID: 21543515 Gene_locus related to this paper: aspna-g3y4g9, aspna-g3yal2, aspna-g3ycq2, aspnc-a2qbh3, aspnc-a2qe77, aspnc-a2qf54, aspnc-a2qfe9, aspnc-a2qg33, aspnc-a2qh76, aspnc-a2qhe2, aspnc-a2qi32, aspnc-a2ql89, aspnc-a2ql90, aspnc-a2qla0, aspnc-a2qmk5, aspnc-a2qn56, aspnc-a2qs22, aspnc-a2qti9, aspnc-a2qtz0, aspnc-a2quc1, aspnc-a2qx92, aspnc-a2qyf0, aspnc-a2qys7, aspnc-a2qz72, aspnc-a2qzn6, aspnc-a2qzr0, aspnc-a2qzx0, aspnc-a2qzx4, aspnc-a2r0p4, aspnc-a2r1r5, aspnc-a2r2i5, aspnc-a2r5r4, aspnc-a2r6h5, aspnc-a2r8r3, aspnc-a2r8z3, aspnc-a2r273, aspnc-a2r496, aspnc-a2r502, aspnc-a5abe5, aspnc-a5abe8, aspnc-a5abh9, aspnc-a5abk1, aspnc-axe1, aspnc-cuti1, aspnc-cuti2, aspng-a2qs46, aspng-a2qv27, aspni-EstA, aspkw-g7y0v7, aspnc-a2qt47, aspnc-a2qt66, aspna-g3xpq9, aspnc-a2qqa1, aspna-g3xsl3, aspna-g3y5a6, aspna-g3xpw9, aspaw-a0a401kpx5, aspnc-a2qw57, aspaw-a0a401kcz4, aspna-alba, aspna-azac Abstract The filamentous fungus Aspergillus niger exhibits great diversity in its phenotype. It is found globally, both as marine and terrestrial strains, produces both organic acids and hydrolytic enzymes in high amounts, and some isolates exhibit pathogenicity. Although the genome of an industrial enzyme-producing A. niger strain (CBS 513.88) has already been sequenced, the versatility and diversity of this species compel additional exploration. We therefore undertook whole-genome sequencing of the acidogenic A. niger wild-type strain (ATCC 1015) and produced a genome sequence of very high quality. Only 15 gaps are present in the sequence, and half the telomeric regions have been elucidated. Moreover, sequence information from ATCC 1015 was used to improve the genome sequence of CBS 513.88. Chromosome-level comparisons uncovered several genome rearrangements, deletions, a clear case of strain-specific horizontal gene transfer, and identification of 0.8 Mb of novel sequence. Single nucleotide polymorphisms per kilobase (SNPs/kb) between the two strains were found to be exceptionally high (average: 7.8, maximum: 160 SNPs/kb). High variation within the species was confirmed with exo-metabolite profiling and phylogenetics. Detailed lists of alleles were generated, and genotypic differences were observed to accumulate in metabolic pathways essential to acid production and protein synthesis. A transcriptome analysis supported up-regulation of genes associated with biosynthesis of amino acids that are abundant in glucoamylase A, tRNA-synthases, and protein transporters in the protein producing CBS 513.88 strain. Our results and data sets from this integrative systems biology analysis resulted in a snapshot of fungal evolution and will support further optimization of cell factories based on filamentous fungi. Title: A novel amperometric biosensor based on single walled carbon nanotubes with acetylcholine esterase for the detection of carbaryl pesticide in water Firdoz S, Ma F, Yue X, Dai Z, Kumar A, Jiang B Ref: Talanta, 83:269, 2010 : PubMed ESTHER: Firdoz_2010_Talanta_83_269 PubMedSearch: Firdoz 2010 Talanta 83 269 PubMedID: 21035674 Abstract Amperometric biosensor is fabricated for the detection of carbaryl based on single walled carbon nanotubes (SWCNTs) and acetylcholine esterase (AchE). The dispersion of SWCNTs in positively charged polyelectrolyte, poly(diallyldimethylammonium chloride) (PDDA), possibly takes place due to weak supramolecular interaction between them, which then binds electrostatically to the negatively charged AchE at pH 7.4 using layer-by-layer (LbL) self-assembly technique. The optical intensity of UV/vis spectra increased with the number of layers, indicating the build up of a multilayer coating on the electrode. The activity of acetylcholine esterase on modified electrode of 3mm in diameter was found to be 0.2U. The biosensor showed good sensitivity and stability towards the monitoring of carbaryl pesticides in water with the detection limit of 10(-12)gL(-1) and recovery of 99.8 +/- 2.7% to 10(-10)gL(-1). This protocol can be used for the immobilization of other enzymes to fabricate a range of biosensors. Title: Differential effects of neurotrophins and schwann cell-derived signals on neuronal survival/growth and synaptogenesis Peng HB, Yang JF, Dai Z, Lee CW, Hung HW, Feng ZH, Ko CP Ref: Journal of Neuroscience, 23:5050, 2003 : PubMed ESTHER: Peng_2003_J.Neurosci_23_5050 PubMedSearch: Peng 2003 J.Neurosci 23 5050 PubMedID: 12832528 Abstract Recent studies have shown that the survival of mammalian motoneurons in vitro is promoted by neurotrophins (NTs) and cAMP. There is also evidence that neurotrophins enhance transmitter release. We thus investigated whether these agents also promote synaptogenesis. Cultured Xenopus spinal cord neurons were treated with a mixture of BDNF, glia-derived neurotrophic factor, NT-3, and NT-4, in addition to forskolin and IBMX or the cell-permeant form of cAMP, to elevate the cAMP level. The outgrowth and survival of neurons were dramatically increased by this trophic stimulation. However, when these neurons were cocultured with muscle cells, the trophic agents resulted in a failure of synaptogenesis. Specifically, the induction of ACh receptor (AChR) clustering in cultured muscle cells was inhibited at nerve-muscle contacts, in sharp contrast to control, untreated cocultures. Because AChR clustering induced by agrin or growth factor-coated beads in muscle cells was unaffected by trophic stimulation, its effect on synaptogenesis is presynaptic in origin. In the control, agrin was deposited along the neurite and at nerve-muscle contacts. This was significantly downregulated in cultures treated with trophic stimuli. Reverse transcriptase-PCR analyses showed that this decrease in agrin deposition was caused by an inhibition of agrin synthesis by trophic stimuli. Both agrin synthesis and induction of AChR clustering were restored under trophic stimulation when Schwann cell-conditioned medium was introduced. These results suggest that trophic stimulation maintains spinal neurons in the growth state, and Schwann cell-derived factors allow them to switch to the synaptogenic state. Title: The actin-driven movement and formation of acetylcholine receptor clusters Dai Z, Luo X, Xie H, Peng HB Ref: Journal of Cell Biology, 150:1321, 2000 : PubMed ESTHER: Dai_2000_J.Cell.Biol_150_1321 PubMedSearch: Dai 2000 J.Cell.Biol 150 1321 PubMedID: 10995438 Abstract A new method was devised to visualize actin polymerization induced by postsynaptic differentiation signals in cultured muscle cells. This entails masking myofibrillar filamentous (F)-actin with jasplakinolide, a cell-permeant F-actin-binding toxin, before synaptogenic stimulation, and then probing new actin assembly with fluorescent phalloidin. With this procedure, actin polymerization associated with newly induced acetylcholine receptor (AChR) clustering by heparin-binding growth-associated molecule-coated beads and by agrin was observed. The beads induced local F-actin assembly that colocalized with AChR clusters at bead-muscle contacts, whereas both the actin cytoskeleton and AChR clusters induced by bath agrin application were diffuse. By expressing a green fluorescent protein-coupled version of cortactin, a protein that binds to active F-actin, the dynamic nature of the actin cytoskeleton associated with new AChR clusters was revealed. In fact, the motive force generated by actin polymerization propelled the entire bead-induced AChR cluster with its attached bead to move in the plane of the membrane. In addition, actin polymerization is also necessary for the formation of both bead and agrin-induced AChR clusters as well as phosphotyrosine accumulation, as shown by their blockage by latrunculin A, a toxin that sequesters globular (G)-actin and prevents F-actin assembly. These results show that actin polymerization induced by synaptogenic signals is necessary for the movement and formation of AChR clusters and implicate a role of F-actin as a postsynaptic scaffold for the assembly of structural and signaling molecules in neuromuscular junction formation. Title: Fluorescence microscopy of calcium and synaptic vesicle dynamics during synapse formation in tissue culture Dai Z, Peng HB Ref: Histochemical Journal, 30:189, 1998 : PubMed ESTHER: Dai_1998_Histochem.J_30_189 PubMedSearch: Dai 1998 Histochem.J 30 189 PubMedID: 10188926 Abstract The signal transduction process involved in the development of the nerve terminal is an intriguing question in developmental neurobiology. During the formation of the neuromuscular junction, presynaptic development is induced by growth cone's contact with the target muscle cell. Fluorescence microscopy with specific markers has made it possible to follow signalling events during this process. By using fluorescent calcium indicators, such as fura-2 and fluo-3, we found that a rise in intracellular calcium is elicited in the growth cone upon its contact with a target, and this calcium signal can also be elicited by local application of basic fibroblast growth factor. To monitor the clustering of synaptic vesicles in response to target contact, the fluorescent vesicular probe FMl-43 was used. With this probe, we observed that packets of synaptic vesicle are already present along the length of naive neurite, which has not encountered its synaptic target. The activity-dependent loading of FMl-43 indicates that these packets can undergo exocytosis and endocytosis upon depolarization. Time-lapse recording showed that these packets are quite mobile. Upon target contact, synaptic vesicles become clustered and immobilized at the contact site. The methodology and instrumentation used in these studies are described in this article. Title: A role of tyrosine phosphatase in acetylcholine receptor cluster dispersal and formation Dai Z, Peng HB Ref: Journal of Cell Biology, 141:1613, 1998 : PubMed ESTHER: Dai_1998_J.Cell.Biol_141_1613 PubMedSearch: Dai 1998 J.Cell.Biol 141 1613 PubMedID: 9647653 Abstract Innervation of the skeletal muscle involves local signaling, leading to acetylcholine receptor (AChR) clustering, and global signaling, manifested by the dispersal of preexisting AChR clusters (hot spots). Receptor tyrosine kinase (RTK) activation has been shown to mediate AChR clustering. In this study, the role of tyrosine phosphatase (PTPase) in the dispersal of hot spots was examined. Hot spot dispersal in cultured Xenopus muscle cells was initiated immediately upon the presentation of growth factor-coated beads that induce both AChR cluster formation and dispersal. Whereas the density of AChRs decreased with time, the fine structure of the hot spot remained relatively constant. Although AChR, rapsyn, and phosphotyrosine disappeared, a large part of the original hot spot-associated cytoskeleton remained. This suggests that the dispersal involves the removal of a key linkage between the receptor and its cytoskeletal infrastructure. The rate of hot spot dispersal is inversely related to its distance from the site of synaptic stimulation, implicating the diffusible nature of the signal. PTPase inhibitors, such as pervanadate or phenylarsine oxide, inhibited hot spot dispersal. In addition, they also affected the formation of new clusters in such a way that AChR microclusters extended beyond the boundary set by the clustering stimuli. Furthermore, by introducing a constitutively active PTPase into cultured muscle cells, hot spots were dispersed in a stimulus- independent fashion. This effect of exogenous PTPase was also blocked by pervanadate. These results implicate a role of PTPase in AChR cluster dispersal and formation. In addition to RTK activation, synaptic stimulation may also activate PTPase which acts globally to destabilize preexisting AChR hot spots and locally to facilitate AChR clustering in a spatially discrete manner by countering the action of RTKs. Title: Association of cortactin with developing neuromuscular specializations Peng HB, Xie H, Dai Z Ref: Journal of Neurocytology, 26:637, 1997 : PubMed ESTHER: Peng_1997_J.Neurocytol_26_637 PubMedSearch: Peng 1997 J.Neurocytol 26 637 PubMedID: 9368878 Abstract During the development of the neuromuscular junction (NMJ), motoneurons grow to the muscle cell and the nerve-muscle contact triggers the development of both presynaptic specialization, consisting of clusters of synaptic vesicles (SVs), and postsynaptic specialization, consisting of clusters of synaptic vesicles (SVs), and postsynaptic specialization, consisting of clusters of acetylcholine receptors (AChRs). Previous studies have shown that the activation of tyrosine kinases and the local assembly of an actin-based cytoskeletal specialization are involved in the development of both types of specializations. To understand the link between tyrosine phosphorylation and the assembly of the cytoskeleton, we examined the localization of cortactin in relationship to synaptic development. Cortactin is a 80/85 kD F-actin binding protein and is a substrate for tyrosine kinases. It contains a proline-rich motif and an SH3 domain and is localized at sites of active F-actin assembly. Using a monoclonal antibody against cortactin, its localization at developing NMJs in culture was observed. To understand the spatial and temporal relationship between cortactin and developing synaptic structures, cultured muscle cells and spinal neurons from Xenopus embryos were treated with beads coated with heparin-binding growth-associated molecule to induce the formation of AChR clusters and SV clusters and the localization of cortactin was followed by immunofluorescence. In untreated muscle cells, cortactin is often co-localized with spontaneously formed AChR clusters. After cells were treated with beads, cortactin became localized at bead-induced AChR clusters at their earliest appearance (1 h after the addition of beads). This association was most reliably detected at the early stage of the clustering process. On the presynaptic side, cortactin localization could be detected as early as 10 min after the bead-neurite contact was established. Cortactin-enriched contacts later showed concentration of F-actin (at 1 h) and clusters of SVs (at 24 h). These data suggest that cortactin mediates the local assembly of the cytoskeletal specialization triggered by the synaptogenic signal on both nerve and muscle. Title: Association of phosphotyrosine with rapsyn expression in Xenopus embryonic cells Dai Z, Scotland PB, Froehner SC, Peng HB Ref: Neuroreport, 7:657, 1996 : PubMed ESTHER: Dai_1996_Neuroreport_7_657 PubMedSearch: Dai 1996 Neuroreport 7 657 PubMedID: 8730851 Abstract The postsynaptic membrane of the neuromuscular junction is highly enriched in rapsyn, which is thought to interact directly with nicotinic acetylcholine receptors (AChR) and anchor them at the synapse. We expressed rapsyn with or without AChRs in Xenopus embryos by mRNA injection. Co-expression of AChR and rapsyn caused the clustering of these two proteins in cultured cells isolated from the injected embryos. When rapsyn was expressed alone, it also became clustered at the substratum-facing membrane in cultured cells and at cell-cell contacts in whole mount embryos. No clusters were observed in cells that expressed AChRs alone. In rapsyn-expressing cells, proteins that are tyrosine phosphorylated as shown by anti-phosphotyrosine antibody labeling were concentrated at rapsyn clusters. Rapsyn itself does not appear to be a substrate for tyrosine kinase. This suggests that other phosphotyrosine-containing proteins are co-clustered with rapsyn in these cells. Title: Dynamics of synaptic vesicles in cultured spinal cord neurons in relationship to synaptogenesis Dai Z, Peng HB Ref: Molecular & Cellular Neurosciences, 7:443, 1996 : PubMed ESTHER: Dai_1996_Mol.Cell.Neurosci_7_443 PubMedSearch: Dai 1996 Mol.Cell.Neurosci 7 443 PubMedID: 8875428 Abstract The dynamics of synaptic vesicles (SVs) during the development of presynaptic specializations in cultured Xenopus spinal cord neurons was studied with the fluorescent vesicular probe FM1-43. In naive neurons that have not contacted synaptic targets, packets of SVs are distributed along the entire neurite and are quite mobile. The interaction with the synaptic target, such as a muscle cell or a latex bead coated with basic fibroblast growth factor, results in the localization and immobilization of SV packets at the contact site. Depolarization resulted in exocytosis of SVs in both naive and target-contacted neurites. Okadaic acid, a phosphatase inhibitor, caused a dispersal of SV packets in both naive and target-contacted neurites. Thus, prior to target contact, SVs are already organized into packets capable of release and recycling by a phosphorylation-dependent mechanism. Target interaction then recruits and anchors these functional SV packets into forming the presynaptic nerve terminal. With fluorescent phalloidin as a probe, F-actin was found to colocalize with SV clusters at bead-neurite contacts. Although okadaic acid caused a dispersal of SVs at the beads, F-actin localization there was relatively resistant to this drug treatment. This suggests that SVs become localized at the target by interacting with an actin-based cytoskeletal specialization in a phosphorylation-sensitive manner. The induction of this cytoskeletal specialization by the target may be an early event in presynaptic differentiation. Title: Clustering of the acetylcholine receptor by the 43-kD protein: involvement of the zinc finger domain Scotland PB, Colledge M, Melnikova I, Dai Z, Froehner SC Ref: Journal of Cell Biology, 123:719, 1993 : PubMed ESTHER: Scotland_1993_J.Cell.Biol_123_719 PubMedSearch: Scotland 1993 J.Cell.Biol 123 719 PubMedID: 8227134 Abstract A postsynaptic membrane-associated protein of M(r) 43,000 (43-kD protein) is involved in clustering of the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction. Previous studies have shown that recombinant mouse 43-kD protein forms membrane-associated clusters when expressed in Xenopus oocytes. Coexpression with the AChR results in colocalization of the receptor with the 43-kD protein clusters (Froehner, S. C., C. W. Luetje, P. B. Scotland, and J. Patrick, 1990. Neuron. 5:403-410). To understand the mechanism of this clustering, we have studied the role of the carboxy-terminal region of the 43-kD protein. The amino acid sequence of this region predicts two tandem zinc finger structures followed by a serine phosphorylation site. Both Torpedo 43-kD protein and the carboxy-terminal region of the mouse 43-kD protein bind radioisotopic zinc. Mutation of two histidine residues in this predicted domain greatly attenuates zinc binding, lending support to the proposal that this region forms zinc fingers. When expressed in oocytes, the ability of this mutant 43-kD protein to form clusters is greatly reduced. Its ability to interact with AChR, however, is retained. In contrast, a mutation that eliminates the potential serine phosphorylation site has no effect on clustering of the 43-kD protein or on interaction with the AChR. These findings suggest that protein interactions via the zinc finger domain of the 43-kD protein may be important for AChR clustering at the synapse. Title: The influence of basic fibroblast growth factor on acetylcholine receptors in cultured muscle cells Dai Z, Peng HB Ref: Neuroscience Letters, 144:14, 1992 : PubMed ESTHER: Dai_1992_Neurosci.Lett_144_14 PubMedSearch: Dai 1992 Neurosci.Lett 144 14 PubMedID: 1331909 Abstract Acetylcholine receptors (AChRs) in Xenopus muscle cells undergo changes in channel kinetics during development in culture and these changes are somehow related to innervation. Recently we showed that basic fibroblast growth factor (bFGF), when locally applied, can mimic the effect of nerve in inducing a postsynaptic-type development. In this study, we examined whether bFGF can influence the developmental changes of AChRs. Patch clamp method was employed to record single AChR channel currents from cultured Xenopus myotomal muscle cells and the kinetics of low-conductance AChR channels were analyzed. In cultures treated with 1 microgram/ml bFGF at an early stage (stage 23), the burst duration of low-conductance AChR channels showed a 1.5-fold decrease between the first and second day in culture, while it underwent a remarkable 3-fold decrease during the same period in the control. Histogram analyses showed that the low-conductance channels were composed of a fast and a slow component and that the decrease in burst duration was due to a shift in the population from the slow to the fast. bFGF treatment appeared to slow down this shift by retaining the slow channels for a longer period of time. This effect is probably not due to channel modulation as the burst duration of short channel in older cells (stage 40) was not affected by bFGF. These data suggest that bFGF may enhance the metabolic stability of intrinsically short-lived AChRs. This effect seems to parallel the stabilization of junctional AChRs at the innervated endplate. Thus, bFGF, or a related polypeptide growth factor, may mediate this and other innervation-induced changes in the postsynaptic membrane. | |||||||
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