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Mol Biol Cell. 2005 Oct;16(10):4609-22. Epub 2005 Jul 19.

APC and EB1 function together in mitosis to regulate spindle dynamics and chromosome alignment.

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1
Section of Molecular and Cellular Biology, University of California-Davis, Davis, CA 95616, USA.

Abstract

Recently, we have shown that a cancer causing truncation in adenomatous polyposis coli (APC) (APC(1-1450)) dominantly interferes with mitotic spindle function, suggesting APC regulates microtubule dynamics during mitosis. Here, we examine the possibility that APC mutants interfere with the function of EB1, a plus-end microtubule-binding protein that interacts with APC and is required for normal microtubule dynamics. We show that siRNA-mediated inhibition of APC, EB1, or APC and EB1 together give rise to similar defects in mitotic spindles and chromosome alignment without arresting cells in mitosis; in contrast inhibition of CLIP170 or LIS1 cause distinct spindle defects and mitotic arrest. We show that APC(1-1450) acts as a dominant negative by forming a hetero-oligomer with the full-length APC and preventing it from interacting with EB1, which is consistent with a functional relationship between APC and EB1. Live-imaging of mitotic cells expressing EB1-GFP demonstrates that APC(1-1450) compromises the dynamics of EB1-comets, increasing the frequency of EB1-GFP pausing. Together these data provide novel insight into how APC may regulate mitotic spindle function and how errors in chromosome segregation are tolerated in tumor cells.

PMID:
16030254
PMCID:
PMC1237068
DOI:
10.1091/mbc.E05-03-0259
[Indexed for MEDLINE]
Free PMC Article
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