Mechanism of RanGTP dependent microtubule assembly during mitosis

During mitosis, spindle assembly involves different sources of microtubules including centrosomes and chromosomes. While the role of centrosomes has been extensively studied, we still do not fully understand how chromosomes trigger microtubule assembly thereby contributing to the formation of the mi...

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Detalles Bibliográficos
Autor: Scrofani, Jacopo
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2014
País:España
Institución:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/289621
Acceso en línea:http://hdl.handle.net/10803/289621
Access Level:acceso abierto
Palabra clave:Cell
Cell cycle
Mitosis
Cell division
Microtubule
Mitotic spindle
Chromosomes
RanGTP
Nucleation
ϒ-tubulin
TPX2
RHAMM
NEDD1
Aurora-A
Xenopus laevis
Phosphorylation
Cicle cel·lular
Divisió cel·lular
Tubulina
Microtúbuls
Fus acromàtic
Ensamblatge del fús
576
Descripción
Sumario:During mitosis, spindle assembly involves different sources of microtubules including centrosomes and chromosomes. While the role of centrosomes has been extensively studied, we still do not fully understand how chromosomes trigger microtubule assembly thereby contributing to the formation of the mitotic spindle. The chromosomal pathway is largely determined by a RanGTP gradient centered on the chromosomes that induces the local activation of spindle assembly factors. To get a better understanding on the RanGTP-dependent microtubule assembly during mitosis we aimed at: i) Identifying new RanGTP regulated proteins involved in spindle assembly. Our results pointed to three novel proteins with a putative mitotic role in the RanGTP pathway. ii) Understanding how the RanGTP pathway regulates microtubule nucleation during mitosis. We found that TPX2 together with Aurora-A and RHAMM are part of a RanGTP-dependent complex that binds and strongly stimulates the -TuRC nucleation activity. iii) Investigating the contribution of the RanGTP pathway to spindle assembly. Our data provided novel evidences that MTs nucleated close to the chromosomes participate in the k-fibers assembly process.