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First published online October 12, 2007
doi: 10.1242/10.1242/dev.010900

Development 134, 3781-3787 (2007)
Published by The Company of Biologists 2007
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Research Report

Asymmetric localisation of Miranda and its cargo proteins during neuroblast division requires the anaphase-promoting complex/cyclosome

Cathy Slack1,*,{dagger}, Paul M. Overton1, Richard I. Tuxworth1 and William Chia1,2,{dagger}

1 MRC Centre for Developmental Neurobiology, New Hunt's House, King's College London, Guy's Campus, London SE1 1UL, UK.
2 Temasek Lifesciences Laboratory and Department of Biological Sciences, 1 Research Link, National University of Singapore, 117604, Singapore.

{dagger} Authors for correspondence (e-mails: c.slack{at}ucl.ac.uk; wchia{at}tll.org.sg)

Accepted 7 August 2007

SUMMARY

Asymmetric cell divisions generate cell fate diversity during both invertebrate and vertebrate development. Drosophila neural progenitors or neuroblasts (NBs) each divide asymmetrically to produce a larger neuroblast and a smaller ganglion mother cell (GMC). The asymmetric localisation of neural cell fate determinants and their adapter proteins to the neuroblast cortex during mitosis facilitates their preferential segregation to the GMC upon cytokinesis. In this study we report a novel role for the anaphase-promoting complex/cyclosome (APC/C) during this process. Attenuation of APC/C activity disrupts the asymmetric localisation of the adapter protein Miranda and its associated cargo proteins Staufen, Prospero and Brat, but not other components of the asymmetric division machinery. We demonstrate that Miranda is ubiquitylated via its C-terminal domain; removal of this domain disrupts Miranda localisation and replacement of this domain with a ubiquitin moiety restores normal asymmetric Miranda localisation. Our results demonstrate that APC/C activity and ubiquitylation of Miranda are required for the asymmetric localisation of Miranda and its cargo proteins to the NB cortex.

Key words: Miranda, Anaphase promoting complex, Asymmetric division, Neuroblast, Drosophila


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Development 2007 134: e2101. [Full Text]  



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© The Company of Biologists Ltd 2007