PT  - JOURNAL ARTICLE
AU  - Chaska C Walton
AU  - Wei Zhang
AU  - Iris Patiño-Parrado
AU  - Estíbaliz Barrio-Alonso
AU  - Juan-José Garrido
AU  - José M Frade
TI  - Checkpoint signaling abrogation after cell cycle reentry reveals that differentiated neurons are mitotic cells
AID  - 10.1101/288589
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 288589
4099  - http://biorxiv.org/content/early/2018/04/17/288589.short
4100  - http://biorxiv.org/content/early/2018/04/17/288589.full
AB  - A belief that has been central to biology for over a century is that neurons are not mitotic. However, how neurons are different from mitotic cells, if at all, remains unanswered. To this end, we have studied the extent to which the cell-cycle machinery of S, G2, and M-phases is functional in differentiated neurons. We have done this by using a fusion protein based on a truncated Cyclin E oncogenic isoform and Cdk2. Oncogenic Cyclin E/Cdk2 expression in primary neurons elicits canonical mitotic checkpoint signaling as in mitotic cells, resulting in cell-cycle arrest and neuronal cell-death. However, checkpoint suppression enables cell-cycle progression through S, G2, and M-phases and neuronal cell-division. We also show that neurons adapt to the cell-cycle by losing and reforming the axon initial segment, a structure essential to maintain neuronal viability. We conclude that neurons are mitotic cells in a reversible quiescent-like state, which is falsely portrayed as irreversible by mitotic checkpoints.