Publications by authors named "Renaud Caous"

5 Publications

  • Page 1 of 1

Aurora A promotes chromosome congression by activating the condensin-dependent pool of KIF4A.

J Cell Biol 2019 02;219(2)

Department of Biochemistry, University of Oxford, Oxford, UK.

Aurora kinases create phosphorylation gradients within the spindle during prometaphase and anaphase, thereby locally regulating factors that promote spindle organization, chromosome condensation and movement, and cytokinesis. We show that one such factor is the kinesin KIF4A, which is present along the chromosome axes throughout mitosis and the central spindle in anaphase. These two pools of KIF4A depend on condensin I and PRC1, respectively. Previous work has shown KIF4A is activated by Aurora B at the anaphase central spindle. However, whether or not chromosome-associated KIF4A bound to condensin I is regulated by Aurora kinases remain unclear. To determine the roles of the two different pools of KIF4A, we generated specific point mutants that are unable to interact with either condensin I or PRC1 or are deficient for Aurora kinase regulation. By analyzing these mutants, we show that Aurora A phosphorylates the condensin I-dependent pool of KIF4A and thus actively promotes chromosome congression from the spindle poles to the metaphase plate.
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http://dx.doi.org/10.1083/jcb.201905194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041678PMC
February 2019

Dual control of Kinesin-1 recruitment to microtubules by Ensconsin in neuroblasts and oocytes.

Development 2019 04 17;146(8). Epub 2019 Apr 17.

Univ. Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes) - UMR 6290, F-35000 Rennes, France

Ensconsin (also known as MAP7) controls spindle length, centrosome separation in brain neuroblasts (NBs) and asymmetric transport in oocytes. The control of spindle length by Ensconsin is Kinesin-1 independent but centrosome separation and oocyte transport require targeting of Kinesin-1 to microtubules by Ensconsin. However, the molecular mechanism used for this targeting remains unclear. Ensconsin contains a microtubule (MT)-binding domain (MBD) and a Kinesin-binding domain (KBD). Rescue experiments show that only full-length Ensconsin restores the spindle length phenotype. KBD expression rescues centrosome separation defects in NBs, but not the fast oocyte streaming and the localization of Staufen and Gurken. Interestingly, the KBD can stimulate Kinesin-1 targeting to MTs and We propose that a KBD and Kinesin-1 complex is a minimal activation module that increases Kinesin-1 affinity for MTs. Addition of the MBD present in full-length Ensconsin allows this process to occur directly on the MT and triggers higher Kinesin-1 targeting. This dual regulation by Ensconsin is essential for optimal Kinesin-1 targeting to MTs in oocytes, but not in NBs, illustrating the importance of adapting Kinesin-1 recruitment to different biological contexts.
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http://dx.doi.org/10.1242/dev.171579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503980PMC
April 2019

Drosophila Aurora A regulates mitotic timing in cancer stem cells: Possible therapeutic implications.

Mol Cell Oncol 2016 May 18;3(3):e1140261. Epub 2016 Feb 18.

Institut de Génétique et Développement de Rennes-Université de Rennes I-CNRS- UMR 6290 , Rennes Cedex, France.

Loss of Aurora A in Drosophila neuroblasts promotes loss of cell fate, leading to brain tumors. We showed that these tumor stem cells are delayed during mitosis and efficiently segregate their chromosomes even without the spindle assembly checkpoint. Here, we discuss the possible relevance of our results to human cancers.
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http://dx.doi.org/10.1080/23723556.2016.1140261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4909412PMC
May 2016

Spindle assembly checkpoint inactivation fails to suppress neuroblast tumour formation in aurA mutant Drosophila.

Nat Commun 2015 Nov 16;6:8879. Epub 2015 Nov 16.

Institut de Génétique et Développement de Rennes-Université de Rennes I-CNRS- UMR 6290, 2 avenue du Pr Léon Bernard, 35043 Rennes, France.

Tissue homeostasis requires accurate control of cell proliferation, differentiation and chromosome segregation. Drosophila sas-4 and aurA mutants present brain tumours with extra neuroblasts (NBs), defective mitotic spindle assembly and delayed mitosis due to activation of the spindle assembly checkpoint (SAC). Here we inactivate the SAC in aurA and sas-4 mutants to determine whether the generation of aneuploidy compromises NB proliferation. Inactivation of the SAC in the sas-4 mutant impairs NB proliferation and disrupts euploidy. By contrast, disrupting the SAC in the aurA mutant does not prevent NB amplification, tumour formation or chromosome segregation. The monitoring of Mad2 and cyclin B dynamics in live aurA NBs reveals that SAC satisfaction is not coupled to cyclin B degradation. Thus, the NBs of aurA mutants present delayed mitosis, with accurate chromosome segregation occurring in a SAC-independent manner. We report here the existence of an Aurora A-dependent mechanism promoting efficient, timed cyclin B degradation.
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http://dx.doi.org/10.1038/ncomms9879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4660220PMC
November 2015

Ensconsin/Map7 promotes microtubule growth and centrosome separation in Drosophila neural stem cells.

J Cell Biol 2014 Mar;204(7):1111-21

Cytoskeleton and Cell Proliferation, 2 Tubulin and Interacting Proteins, and 3 Spatio-temporal Regulation of Transcription, Biosit, Université de Rennes I, Centre National de la Recherche Scientifique, UMR 6290, 35043 Rennes, France.

The mitotic spindle is crucial to achieve segregation of sister chromatids. To identify new mitotic spindle assembly regulators, we isolated 855 microtubule-associated proteins (MAPs) from Drosophila melanogaster mitotic or interphasic embryos. Using RNAi, we screened 96 poorly characterized genes in the Drosophila central nervous system to establish their possible role during spindle assembly. We found that Ensconsin/MAP7 mutant neuroblasts display shorter metaphase spindles, a defect caused by a reduced microtubule polymerization rate and enhanced by centrosome ablation. In agreement with a direct effect in regulating spindle length, Ensconsin overexpression triggered an increase in spindle length in S2 cells, whereas purified Ensconsin stimulated microtubule polymerization in vitro. Interestingly, ensc-null mutant flies also display defective centrosome separation and positioning during interphase, a phenotype also detected in kinesin-1 mutants. Collectively, our results suggest that Ensconsin cooperates with its binding partner Kinesin-1 during interphase to trigger centrosome separation. In addition, Ensconsin promotes microtubule polymerization during mitosis to control spindle length independent of Kinesin-1.
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http://dx.doi.org/10.1083/jcb.201311094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3971751PMC
March 2014