Platelet activating factor blocks interkinetic nuclear migration in retinal progenitors through an arrest of the cell cycle at the S/G2 transition.

ABSTRACT: Nuclear migration is regulated by the LIS1 protein, which is the regulatory subunit of platelet activating factor (PAF) acetyl-hydrolase, an enzyme complex that inactivates the lipid mediator PAF. Among other functions, PAF modulates cell proliferation, but its effects upon mechanisms of the cell cycle are unknown. Here we show that PAF inhibited interkinetic nuclear migration (IKNM) in retinal proliferating progenitors. The lipid did not, however, affect the velocity of nuclear migration in cells that escaped IKNM blockade. The effect depended on the PAF receptor, Erk and p38 pathways and Chk1. PAF induced no cell death, nor a reduction in nucleotide incorporation, which rules out an intra-S checkpoint. Notwithstanding, the expected increase in cyclin B1 content during G2-phase was preven

SUBMITTER: Fragel-Madeira L 

PROVIDER: S-EPMC3029264 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature