AURORA A IN MITOSIS · Role of Aurora A kinase in establishment and maintainance of spindle bipolarity during mitosis
6РП — Действия „Мария Кюри“
- Период
- 2007-04-01 → 2009-03-31
- Финансиране от ЕС
- 177 799 €
- Участници
- 1
- Схема
- EIF
Линиите свързват координатора с партньорите.
Накратко на български
Ролята на протеина Klp10A при контрола на дължината на центриолите се проучва чрез опити с плодови мухи. Това помага да се разбере как се предотвратява разпадането на центрозомите, което е важно за правилното делене на клетките, репродукцията и работата на нервната система.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - AURORA A IN MITOSIS (Role of Aurora A kinase in establishment and maintainance of spindle bipolarity during mitosis)
Centrioles are cylindrical structures, the walls of which are composed of microtubules. Two centrioles arranged orthogonally and surrounded by a dense cloud of proteins form the centrosome. The centrosome is the main centre for nucleation of microtubules. Our work identified a new component, Klp10A, localised along the centriole and enriched on its ends. When levels of Klp10A are greatly reduced at this location, longer, broken and fragments of centrioles are observed in the cells of Drosophila testes at various stages of mitotic and meiotic divisions. Moreover, flies depleted for Klp10A are uncoordinated and sterile. Uncoordination and sterility are generally a consequence of defective ciliated cells of the nervous system and defective germ lines. Longer and damaged centrioles are also detected in Drosophila cultured cells depleted for klp10A. Depolymerisation of microtubules by Klp10A has been previously shown to be responsible for the shortening of the microtubules in interphase cells and for controlling the length of the mitotic spindle. Our results show that the formation of overly long centrioles is also directly linked to the microtubule depolymerising activity of Klp10A. These elongated centrioles would then fragment when submitted to elevated tension of microtubules motors on centrosomes during mitosis. Thus, in addition to regulating the length of cytoplasmic microtubules, Klp10A controls also the length of centriole microtubules. This is necessary to avoid the generation of multipolar spindles due to centrosomal fragmentation and to retain the capacity to nucleate asters or to keep centrioles and so generate basal bodies, cilia and flagella.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
To be faithfully transmitted during cell division, chromosomes segregate on the mitotic spindle. The spindle assembles by the separation and migration of the two centrosomes nucleating microtubules either side of the condensed chromosomes. Aurora A kinase, whose gene is a human cancer susceptibility gene, appears necessary for correct spindle assembly. Nevertheless, how it orchestrates the process is not fully understood.We propose to study roles of Aurora A in regulating spindle function through motor com plexes and microtubules associated proteins responsible for the migration of centrosomes. The aim of this project is first to analyse the defects in mitotic spindle formation in living drosophila embryo mutant for Aurora A or injected with Aurora A inhibitors (molecules tested as anti-cancer agents in pre-clinical studies at Cyclacel Ltd).Secondly, I will study the role of Aurora A phosphorylation on potential substrates of the kinase associated with microtubules. I will use mass spectrometry to identify the phosphorylation sites. I will then mutate these sites and determine the effects upon assembly of the mitotic spindle. This project fits to a thematic priority of the FP6 program, namely to combat cancer.The combined use of embryo imaging, Drosophila genetics and biochemistry will allow us to understand fundamentals of a biological process of therapeutic interest in cancer treatment. The main skills required for this project are totally new for me as my former experience was in the characterisation of the IGF-1 signal transduction pathway by means of biochemical and cellular biological approaches in Huntingtons disease.Thus I am switching fields and joining a leading cell cycle group where I will become familiar with new methods and techniques. The opportunity to carry out my postdoctoral training at the University of Cambridge places me in a renowned and stimulating scientific environment that will be of great benefit to my growth as a scientist.
Оригинален текст от CORDIS (на английски).
Участници
- University of Cambridge · CambridgeКоординаторОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз