Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A major determinant of neuronal morphology is the cytoskeleton. And one of the main regulatory mechanisms of cytoskeletal proteins is the modification of their phosphorylation state via changes in the relative activities of protein kinases and phosphatases in neurons. In particular, the microtubule-associated protein 2 (MAP2) family of proteins are abundant cytoskeletal components predominantly expressed in neurons and have been found to be substrates for most of protein kinases and phosphatases present in neurons, including glycogen-synthase kinase 3 (GSK3). It has been suggested that changes in GSK3-mediated MAP phosphorylation may modify MT stability and could control neuronal development. We have previously shown that MAP2 is phosphorylated in vitro and in situ by GSK3 at Thr1620 and Thr1623, located in the proline-rich region of MAP2 and recognized by antibody 305. However, the function of the phosphorylation of this site of MAP2 is still unknown. In this study, non-neuronal COS-1 cells have been co-transfected with cDNAs encoding MAP2C and either wild type or mutated GSK3beta to analyze possible effects on microtubule stability and on the association of MAP2 with microtubules. We have found that GSK3beta phosphorylates MAP2C in co-transfected cells. Moreover, this phosphorylation is inhibited by the specific GSK3 inhibitor lithium chloride. Additionally, the formation of microtubule bundles, which is observed after transfection with MAP2C, was decreased when MAP2C was co-transfected with GSK3beta wild type. Microtubule bundles were not observed in cells expressing MAP2C phosphorylated at the site recognized by antibody 305. The absence of microtubule bundles was reverted after treatment of MAP2C/GSK3beta wild type transfected cells with lithium chloride. Highly phosphorylated MAP2C species, which were phosphorylated at the site recognized by antibody 305, appeared in cells co-transfected with MAP2C and GSK3beta wild type. Interestingly, these MAP2C species were enriched in cytoskeleton-unbound protein preparations. These data suggests that GSK3-mediated phosphorylation of MAP2 may modify its binding to microtubules and regulate microtubule stability.
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PMID:GSK3beta-mediated phosphorylation of the microtubule-associated protein 2C (MAP2C) prevents microtubule bundling. 1082 93

The sensitivity of microtubules (MTs) to methylmercury- (MeHg) induced disassembly was compared in undifferentiated, MAP1A- and MAP2C-transfected, and neuronally differentiated P19 Embyronal Carcinoma (EC) cells. The extent of MT disassembly was examined qualitatively by immunofluorescence microscopy and Western blotting and quantitatively by dot blotting of polymer and soluble proteins extracts. Immunofluorescence microscopy showed that MeHg disassembled MTs in a time- and dose-dependent manner and that MTs in both MAP2C-transfected and neuronally differentiated cells, but not those in MAP1A-transfected cells, were significantly more resistant to MeHg-induced MT depolymerization than those in undifferentiated cells. These results suggest that MAP2C has a greater ability to stabilize MTs against MeHg-induced disassembly than MAP1A. Surprisingly, however, when the extent of MT disassembly was assessed by Western blotting and by quantitative dot blotting, no change was observed in the amounts of tubulin, MAP2, or MAP1A, in the polymer and soluble fractions in MeHg-treated samples, compared to the control cells that were not treated. These data show that, although MeHg treatment resulted in the disassembly of MTs, they were not depolymerized as detergent-soluble subunits, but rather appeared to form insoluble tubulin-MAP oligomers or aggregates.
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PMID:Effects of microtubule-associated protein (MAP) expression on methylmercury-induced microtubule disassembly. 1090 84