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

• DOI: 10.1016/j.celrep.2018.04.083
• Publication Date: 2018-05-22T14:44:37Z
• Authors: Giovanni Morelli; Aviel Even; Ivan Gladwyn-Ng; Romain Le Bail; Michal Shilian; Juliette D. Godin; Elise Peyre; Bassem A. Hassan; Arnaud Besson; Jean-Michel Rigo; Miguel Weil; Bert Brône; Laurent Nguyen
• Keywords: Male; 0301 basic medicine; QH301-705.5; [SDV]Life Sciences [q-bio]; p27(Kip1); ATAT1; Motor Activity; Histone Deacetylase 6; Axonal Transport; Microtubules; Models, Biological; Mice; 03 medical and health sciences; Acetyltransferases; p27Kip1; dacapo; acetylation; axonal transport; ATAT1; alpha-tubulin; HDAC6; Drosophila; mouse; cerebral cortex; Enzyme Stability; Animals; Drosophila Proteins; Humans; Biology (General); mouse; acetylation; Neurons; dacapo; Nuclear Proteins; Acetylation; HDAC6; Drosophila melanogaster; HEK293 Cells; alpha-tubulin; Microtubule Proteins; cerebral cortex; Drosophila; Female; axonal transport; Cyclin-Dependent Kinase Inhibitor p27

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.