title: p600 stabilizes microtubules to prevent the aggregation of CaMKIIα during photoconductive stimulation.
abstract: The large microtubule-associated/Ca(2+)-signalling protein p600 (also known as UBR4) is required for hippocampal neuronal survival upon Ca(2+) dyshomeostasis induced by glutamate treatment. During this process, p600 prevents aggregation of the Ca(2+)/calmodulin-dependent kinase IIα (CaMKIIα), a proxy of neuronal death, via direct binding to calmodulin in a microtubuleindependent manner. Using photoconductive stimulation coupled with live imaging of single neurons, we identified a distinct mechanism of prevention of CaMKIIα aggregation by p600. Upon direct depolarization, CaMKIIα translocates to microtubules. In the absence of p600, this translocation is interrupted in favour of a sustained self-aggregation that is prevented by the microtubule-stabilizing drug paclitaxel. Thus, during photoconductive stimulation, p600 prevents the aggregation of CaMKIIα by stabilizing microtubules. The effectiveness of this stabilization for preventing CaMKIIα aggregation during direct depolarization but not during glutamate treatment suggests a model wherein p600 has two modes of action depending on the source of cytosolic Ca(2+).
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Departments of Clinical Neurosciences, Cell Biology & Anatomy, Biochemistry & Molecular Biology, 3330 Hospital Drive NW, Calgary, Alberta, Canada, T2N 4N1.
authors.forename: Camille
authors.initials: C
authors.lastname: Belzil
authors.forename: Tim
authors.initials: T
authors.lastname: Ramos
authors.forename: Kamon
authors.initials: K
authors.lastname: Sanada
authors.forename: Michael A
authors.initials: MA
authors.lastname: Colicos
authors.forename: Minh Dang
authors.initials: MD
authors.lastname: Nguyen
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D008027:Light; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D034622:RNA Interference; D051381:Rats; D059010:Single-Cell Analysis / Q000379:methods; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D008869:Microtubule-Associated Proteins; D044767:Ubiquitin-Protein Ligases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C000598880:UBR4 protein, rat