p27Kip1 Modulates Axonal Transport by Regulating α-Tubulin Acetyltransferase 1 Stability - Archive ouverte HAL
Journal Articles Cell Reports Year : 2018

p27Kip1 Modulates Axonal Transport by Regulating α-Tubulin Acetyltransferase 1 Stability

Giovanni Morelli
  • Function : Author
Aviel Even
  • Function : Author
Ivan Gladwyn-Ng
  • Function : Author
Romain Le Bail
  • Function : Author
Michal Shilian
  • Function : Author
Elise Peyre
  • Function : Author
Jean-Michel Rigo
  • Function : Author
Miguel Weil
  • Function : Author
Bert Brône
  • Function : Author
Laurent Nguyen

Abstract

The protein p27Kip1 plays roles that extend beyond cell-cycle regulation during cerebral cortex development, such as the regulation of neuronal migration and neurite branching via signaling pathways that converge on the actin and microtubule cytoskeletons. Microtubule-dependent transport is essential for the maturation of neurons and the establishment of neuronal connectivity though synapse formation and maintenance. Here, we show that p27Kip1 controls the transport of vesicles and organelles along the axon of mice cortical projection neurons in vitro. Moreover, suppression of the p27Kip1 ortholog, dacapo, in Drosophila melanogaster disrupts axonal transport in vivo, leading to the reduction of locomotor activity in third instar larvae and adult flies. At the molecular level, p27Kip1 stabilizes the α-tubulin acetyltransferase 1, thereby promoting the acetylation of microtubules, a post-translational modification required for proper axonal transport.
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hal-01812608 , version 1 (11-06-2018)

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Giovanni Morelli, Aviel Even, Ivan Gladwyn-Ng, Romain Le Bail, Michal Shilian, et al.. p27Kip1 Modulates Axonal Transport by Regulating α-Tubulin Acetyltransferase 1 Stability. Cell Reports, 2018, 23 (8), pp.2429 - 2442. ⟨10.1016/j.celrep.2018.04.083⟩. ⟨hal-01812608⟩
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