Of JNK with SP600125 decreasesDiscussionHere we show that Wnt-Dvl signalling regulates

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asked Jun 28 in Maths by sudananger52 (270 points)
The scaffold <a href="http://www.chemscene.com/729607-74-3.html">CS-0493 web</a> protein Dvl is tightly associated with MTs [4] and increases MT <a href="http://www.chemscene.com/163521-12-8.html">Vilazodone chemical information</a> stability through the local inhibition of a pool of Gsk3 [5]. In turn, inhibition of Gsk3 by Wnt or <a href="http://www.chemscene.com/1032568-63-0.html">1032568-63-0 site</a> expression of Dvl leads to changes in the phosphorylation of MAPs, <a href="http://www.chemscene.com/355025-24-0.html">355025-24-0 chemical information</a> notably MAP1B, resulting in increased MT stability. B) Quantification shows that neurons expressing DIX or PDZ mutants and treated with SP600125 exhibit the same low level of MT stability as untreated neurons. Conversely, neurons expressing DEP-Dvl mutant and treated with SP600125 show lower level of MT stability than control untreated neurons. C) Full length Dvl and DEP-Dvl bind to MTs along the axon whereas low levels of PDZ-Dvl mutant remains associated to MTs after detergent fixation. Scale bar 15 m. Three asterisks, P < 0.001.Page 9 of(page number not for citation purposes)BMC Cell Biology 2007, 8:http://www.biomedcentral.com/1471-2121/8/Figure 6 Dvl signals through two parallel pathways to regulate microtubule stability by Dvl Dvl signals through two parallel pathways to regulate microtubule stability by Dvl. A) Neurons expressing Dvl an Gsk3 and treated with JNK inhibitor lose the residual level of MTs when compare with neurons expressing Dvl and Gsk3. Scale bar 15 m. B) Quantification shows that neurons expressing Dvl and Gsk3 and treated with JNK inhibitor have a decreased level of MTs <a href="https://www.ncbi.nlm.nih.gov/pubmed/28199957" title=View Abstract(s)">PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28199957</a> stability than untreated neurons expressing Dvl and Gsk3. C) Quantification shows that neurons expressing Dvl together with Gsk3 and treated with Anisomicin have comparable level of MT stability as untreated neurons. D) Inhibition of JNK by expression of JBD does not affect the level of phosphorylated MAP1B in granule cell neurons expressing Dvl when compared to control neurons expressing Dvl alone (arrow). Scale bar 10 m. Two asterisks, P < 0.01; Three asterisks, P < 0.001.Page 10 of(page number not for citation purposes)BMC Cell Biology 2007, 8:http://www.biomedcentral.com/1471-2121/8/expression of Dvl.Of JNK with SP600125 decreasesDiscussionHere we show that Wnt-Dvl signalling regulates MT dynamics through two distinct pathways. Dvl induces the concomitant inhibition of Gsk3 and the activation of JNK to increase MT stability. The typical PCP pathway appears not to be involved as small Rho GTPases are not required for this function. These findings highlight a new role for JNK kinase in the modulation of the MT dynamics mediated by Wnt signaling. We have previously showed that a divergent canonical Wnt pathway regulates MT dynamics. The scaffold protein Dvl is tightly associated with MTs [4] and increases MT stability through the local inhibition of a pool of Gsk3 [5]. In turn, inhibition of Gsk3 by Wnt or expression of Dvl leads to changes in the phosphorylation of MAPs, notably MAP1B, resulting in increased MT stability. Although pharmacological inhibition of Gsk3 increases MT stability, this effect is weaker than that observed byPage 8 of(page number not for citation purposes)BMC Cell Biology 2007, 8:http://www.biomedcentral.com/1471-2121/8/Figure 5 The PDZ domain and at lesser extent the DIX domains of Dvl are required for activation of JNK The PDZ domain and at lesser extent the DIX domains of Dvl are required for activation of JNK.

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