Cdk1, Plks, Auroras, and Neks: the mitotic bodyguards.

In: Li JJ, Li SA, Mohla S, Rochefort H, Maudelonde T, (eds), 2008, Hormonal Carcinogenesis V : Proceedings of the Fifth International Symposium, New York, Springer-Verlag. (Adv. Exp. Med. Biol. 617)International audienceThe coordination of progression through mitosis is mainly orchestrated by protein phosphorylation insured by several serine/threonine kinases. In this short review we will focus on the four main mitotic kinase families: the cyclin-dependent kinase: Cdks, the polo-like kinases: Plks, the Aurora kinases and the NIMArelated kinases: Nerks

Modelling paralytic shellfish toxins (PST) accumulation in Crassostrea gigas by using Dynamic Energy Budgets (DEB)

As other filter-feeders, Crassostrea gigas can concentrate paralytic shellfish toxins (PST) by consuming dinoflagellate phytoplankton species like Alexandrium minutum. Intake of PST in oyster tissues mainly results from feeding processes, i.e. clearance rate, pre-ingestive sorting and ingestion that are directly influenced by environmental conditions (trophic sources, temperature). This study aimed to develop a mechanistic model coupling the kinetics of PST accumulation and bioenergetics in C. gigas based on Dynamic Energy Budget (DEB) theory. For the first time, the Synthesizing Units (SU) concept was applied to formalize the feeding preference of oysters between non-toxic and toxic microalgae. Toxin intake and accumulation were both dependent on the physiological status of oysters. The accumulation was modelled through the dynamics of two toxin compartments: (1) a compartment of ingested but non-assimilated toxins, with labile toxins within the digestive gland eliminated via faeces production; (2) a compartment of assimilated toxins with a rapid detoxification rate (within a few days). Firstly, the DEB-PST model was calibrated using data from two laboratory experiments where oysters have been exposed to A. minutum. Secondly, it was validated using data from another laboratory experiment and from three field surveys carried out in the Bay of Brest (France) from 2012 to 2014. To account for the variability in PST content of A. minutum cells, the saxitoxin (STX) amount per energy units in a toxic algae (ρPST) was adjusted for each dataset. Additionally, the effects of PST on the oyster bioenergetics were calibrated during the first laboratory experiment. However, these effects were shown to depend on the strain of A. minutum. Results of this study could be of great importance for monitoring agencies and decision makers to identify risky conditions (e.g. production areas, seawater temperature), to properly assess detoxification step (e.g. duration, modalities) before any commercialization or to improve predictions regarding closing of shellfish areas

Mnk1 kinase activity is required for abscission.

International audienceMnk1 is a serine/threonine kinase identified as a target for MAP kinase pathways. Using chemical drug, kinase-dead expression or knock down by RNA interference, we show that inhibition of Mnk1 induces the formation of multinucleated cells, which can be rescued by expressing an RNA interference resistant form of Mnk1. We found that active human Mnk1 localises to centrosomes, spindle microtubules and the midbody. Time-lapse recording of Mnk1 depleted cells display cytokinesis defects, as daughter cells fuse back together. Under inhibition of Mnk1 activity, no microtubule defect at the midbody was detected, however membrane vesicles anchorage at the midbody was impaired as lumenal-GFP positive-vesicles did not accumulate at the midbody. At the molecular level, we found that centriolin localisation was impaired at the midbody in Mnk1 depleted cells. As a consequence endobrevin, a V-SNARE protein implicated in the abscission step, was not properly localised at the midbody. Altogether our data show that Mnk1 activity is required for abscission

Localization of aurora A and aurora B kinases during interphase: role of the N-terminal domain.: Interphase localization of Aurora kinases A and B

International audienceAurora kinases possess a conserved catalytic domain (CD) and a N-terminal domain (ND) that varies in size and sequence. We have previously reported that the N-terminal domain of AuroraA (AurA) participates in the localization of the kinase to the centrosome in interphase. AuroraB (AurB) is a chromosome passenger protein and its N-terminal domain is not necessary for its localization or function during mitosis. Using various combinations of GFP-AurA and AurB protein domains we show that AurB N-terminal domain is required for nuclear localization in Xenopus XL2 cells in interphase. In human cells, however, we found both AurA and AurB kinases in the nucleus, AurA being mainly cytoplasmic and AurB mainly nuclear. Both proteins are actively excluded from the nucleus by a CRM1 dependent pathway. Interestingly, at a functional level, in interphase, every combination of Aurora kinase domains (ND-CD) rescues histone H3 Serine10 phosphorylation defect induced by AurB knockdown. This clearly indicates the presence of a functional AurA in the nucleus. However, the chimera ND-AurA/CD-AurB was much more efficient than the ND-AurB/ CD-AurA to rescue multinucleation also induced by AurB knockdown. This indicates that the catalytic domain of AurB is required to fulfill specific functions during mitosis that cannot be fulfilled by the catalytic domain of AurA, probably for localization reasons during mitosis