title: 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 prevented in the proliferating cells. We conclude that PAF blocks interkinetic nuclear migration in retinal progenitor cells through an unusual arrest of the cell cycle at the transition from S to G2 phases. These data suggest the operation, in the developing retina, of a checkpoint that monitors the transition from S to G2 phases of the cell cycle.
authors.affiliation: Institute of Biophysics, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Lucianne
authors.initials: L
authors.lastname: Fragel-Madeira
authors.forename: Tamara
authors.initials: T
authors.lastname: Meletti
authors.forename: Rafael M
authors.initials: RM
authors.lastname: Mariante
authors.forename: Robson Q
authors.initials: RQ
authors.lastname: Monteiro
authors.forename: Marcelo
authors.initials: M
authors.lastname: Einicker-Lamas
authors.forename: Robson R
authors.initials: RR
authors.lastname: Bernardo
authors.forename: Angela H
authors.initials: AH
authors.lastname: Lopes
authors.forename: Rafael
authors.initials: R
authors.lastname: Linden
mesh_terms: D000818:Animals; D001692:Biological Transport; D002467:Cell Nucleus / Q000502:physiology*; D049109:Cell Proliferation; D000071877:Checkpoint Kinase 1; D048049:Extracellular Signal-Regulated MAP Kinases; D016195:G2 Phase; D010972:Platelet Activating Factor / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D011494:Protein Kinases; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D012160:Retina / Q000166:cytology; D016196:S Phase; D013234:Stem Cells; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1; C000605871:Chek1 protein, rat; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases