Dissecting the function and assembly of acentriolar microtubule organizing centers in Drosophila cells in vivo

Acentriolar microtubule organizing centers (aMTOCs) are formed during meiosis and mitosis in several cell types, but their function and assembly mechanism is unclear. Importantly, aMTOCs can be overactive in cancer cells, enhancing multipolar spindle formation, merotelic kinetochore attachment and a...

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Bibliographic Details
Published in:PLoS genetics 2015-05, Vol.11 (5), p.e1005261-e1005261
Main Authors: Baumbach, Janina, Novak, Zsofia Anna, Raff, Jordan W, Wainman, Alan
Format: Article
Language:English
Subjects:
Animals
Brain research
Cancer
Cell cycle
Cell division
Centrioles - genetics
Centrosome - metabolism
Drosophila
Drosophila melanogaster
Genetic aspects
Insects
Kinesin - genetics
Kinesin - metabolism
Medical research
Meiosis
Meiosis - genetics
Microtubule-Organizing Center
Microtubules
Microtubules - genetics
Microtubules - metabolism
Mitosis - genetics
Physiological aspects
Proteins
Spindle Apparatus - genetics
Spindle Poles - genetics
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Summary:Acentriolar microtubule organizing centers (aMTOCs) are formed during meiosis and mitosis in several cell types, but their function and assembly mechanism is unclear. Importantly, aMTOCs can be overactive in cancer cells, enhancing multipolar spindle formation, merotelic kinetochore attachment and aneuploidy. Here we show that aMTOCs can form in acentriolar Drosophila somatic cells in vivo via an assembly pathway that depends on Asl, Cnn and, to a lesser extent, Spd-2--the same proteins that appear to drive mitotic centrosome assembly in flies. This finding enabled us to ablate aMTOC formation in acentriolar cells, and so perform a detailed genetic analysis of the contribution of aMTOCs to acentriolar mitotic spindle formation. Here we show that although aMTOCs can nucleate microtubules, they do not detectably increase the efficiency of acentriolar spindle assembly in somatic fly cells. We find that they are required, however, for robust microtubule array assembly in cells without centrioles that also lack microtubule nucleation from around the chromatin. Importantly, aMTOCs are also essential for dynein-dependent acentriolar spindle pole focusing and for robust cell proliferation in the absence of centrioles and HSET/Ncd (a kinesin essential for acentriolar spindle pole focusing in many systems). We propose an updated model for acentriolar spindle pole coalescence by the molecular motors Ncd/HSET and dynein in conjunction with aMTOCs.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1005261