Biology subjects

Metivier, M.

Publications and source records attributed to Metivier, M..

3 recordsLinked to original sources

bioRxiv2021

Aurora kinases promote mitotic progression and asymmetric cell division through activation of Polo kinase

The maintenance of a restricted pool of asymmetrically dividing stem cells is essential for tissue homeostasis. This process requires the control of mitotic progression that ensures the accurate chromosome segregation. In addition, this event is coupled to the asymmetric distribution of cell fate determinants in order to prevent stem cell amplification. How this coupling is regulated remains poorly described. Here, using asymmetrically dividing Drosophila neural stem cells (NSCs), we show that Polo kinase activity levels determine the length of cell division, independent of the spindle assembly checkpoint (SAC). This event is mediated by the direct phosphorylation of Polo kinase by Aurora A at spindle poles and Aurora B kinases at centromeres. Furthermore, we show that Aurora A-dependent activation of Polo is the major event that promotes NSC polarization and together with the SAC prevents brain tumor growth. Altogether, our results show that an Aurora/Polo kinase module couples NSC mitotic progression and polarization for tissue homeostasis.

cell biology↗

bioRxiv2020

Drosophila dTBCE recruits tubulin around chromatin to promote mitotic spindle assembly

Proper assembly of mitotic spindles requires microtubule nucleation at centrosomes but also around chromatin. In this study, we reveal a novel mechanism by which an enrichment of tubulin in the nuclear space following nuclear envelope breakdown promotes nucleation of spindle microtubules. This event mediated by the tubulin-specific chaperone dTBCE, depends on its tubulin binding CAP-Gly motif and is regulated by Ran. Live imaging, proteomic and biochemical analyses suggest that dTBCE is enriched in the nucleus at nuclear envelope breakdown and interacts with nuclear pore proteins and the Ran machinery to create an environment that facilitates subsequent tubulin enrichment. We propose that dTBCE-dependent increase in tubulin concentration in the nuclear space is an important mechanism for microtubule nucleation in organisms where compartmentalization prevents free diffusion of tubulin.

cell biology↗

bioRxiv2018

The Kinesin-1 binding domain of Ensconsin/MAP7 promotes Kinesin-1 activation in vivo

Centrosome separation in Drosophila larval neuroblasts and asymmetric transport of embryonic determinants in oocytes are both microtubule-dependent processes that require Kinesin-1 activation by Ensconsin/microtubule-associated protein 7 (MAP7). However, the molecular mechanism used by Ensconsin to activate Kinesin-1 remains elusive. Ensconsin/ MAP7 contains an N-terminal microtubule-binding domain (MBD) and a C-terminal Kinesin-binding domain (KBD). Using rescue experiments in live flies, we show that KBD expression alone is sufficient to fully rescue Ensconsin-dependent centrosome separation defects, but not the fast oocyte streaming and the localization patterns of Staufen and Gurken proteins. Interestingly, we show here for the first time that KBD binds and stimulates Kinesin-1 binding to Mts in vivo and in vitro. We propose that the KBD/Kinesin-1 motor represents a minimal activation module that stimulates Kinesin-1 binding to Mts. Addition of the MBD, present in the full length Ensconsin allows this activation to occur directly on the Mt. Our data also suggest that in a very large cell with a complex microtubule network, but not in smaller cells, this dual activation by Ensconsin is essential for optimal Kinesin-1 targeting to the microtubule cytoskeleton.

cell biology↗