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Crumbs interacts with Xpd for nuclear division control in Drosophila

Oncogene volume 34, pages 2777–2789 (2015)Cite this article

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Abstract

Crumbs (Crb) family proteins are crucial for cell polarity. Recent studies indicate that they are also involved in growth regulation and cancer. However, it is not well-understood how Crb participates in mitotic processes. Here, we report that Drosophila Crb is critically involved in nuclear division by interacting with Xeroderma pigmentosum D (XPD). A novel gene named galla-1 was identified from a genetic screen for crb modifiers. Galla-1 protein shows homology to MIP18, a subunit of the mitotic spindle-associated MMS19–XPD complex. Loss-of-function galla-1 mutants show abnormal chromosome segregation, defective centrosome positions and branched spindles during nuclear division in early embryos. Embryos with loss-of-function or overexpression of crb show similar mitotic defects and genetic interaction with galla-1. Both Galla-1 and Crb proteins show overlapping localization with spindle microtubules during nuclear division. Galla-1 physically interacts with the intracellular domain of Crb. Interestingly, Galla-1 shows little binding to the Drosophila homolog of XPD, but a related protein Galla-2 binds both Crb and Xpd. Loss-of-function galla-2 mutants show similar mitotic defects as galla-1 and strong genetic interaction with crb. Xpd can form a physical complex with Crb. In imaginal disc, Crb overexpression causes tissue overgrowth as well as DNA damages marked by H2Av phosphorylation. These phenotypes are suppressed by reduction of Xpd. Taken together, this study identifies a novel Crb–Galla–Xpd complex and its function for proper chromosome segregation during nuclear division, implicating a potential link between Crb and Xpd-related genome instability.

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Acknowledgements

We are grateful to Kyung-Ok Cho, Sang-Chul Nam and Walton Jones for critical comments on the manuscript. We thank Beat Suter and Tom Kaufmann for xpd mutant and anti-centrosomin antibody, respectively. We also thank Yang Hong for Crb::GFP and crb mutant alleles. We acknowledge the Bloomington Drosophila Stock Center, the National Institute of Genetics stock center and the Developmental Studies Hybridoma Bank for fly stocks and antibodies. This research was supported by grants from the World Class University Program (R31-2008-000-10071-0), the National President Fellowship (35B-2011-1-C00033) and the National Research Laboratory grant (NRF-2011-0028326) through the National Research Foundation of Korea funded by the Ministry of Education, Science & Technology.

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Authors and Affiliations

  1. Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea

    E Yeom, S-T Hong & K-W Choi

  2. Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology, Daejeon, Korea

    K-W Choi

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Correspondence to K-W Choi.

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Yeom, E., Hong, ST. & Choi, KW. Crumbs interacts with Xpd for nuclear division control in Drosophila. Oncogene 34, 2777–2789 (2015). https://doi.org/10.1038/onc.2014.202

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