Open Access

p600 stabilizes microtubules to prevent the aggregation of CaMKIIα during photoconductive stimulation

  • Camille Belzil1,
  • Tim Ramos1,
  • Kamon Sanada2,
  • Michael A. Colicos1 and
  • Minh Dang Nguyen1Email author
Cellular & Molecular Biology LettersAn International Journal201419:201

https://doi.org/10.2478/s11658-014-0201-9

Received: 1 March 2014

Accepted: 7 July 2014

Published: 18 July 2014

Abstract

The large microtubule-associated/Ca2+-signalling protein p600 (also known as UBR4) is required for hippocampal neuronal survival upon Ca2+ dyshomeostasis induced by glutamate treatment. During this process, p600 prevents aggregation of the Ca2+/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 Ca2+.

Keywords

P600UBR4Ca2+ Ca2+/calmodulin-dependent kinase IIαMicrotubulesPaclitaxel

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