Critical role for the EB1 and APC interaction in the regulation of microtubule polymerization

Masafumi Nakamura, Xiao Zhen Zhou, Kun Ping Lu

Research output: Contribution to journalArticle

151 Citations (Scopus)

Abstract

Human EB1 was originally cloned as a protein that interacts with the COOH terminus of adenomatous polyposis coli (APC) [1]. Interestingly, this interaction is often disrupted in colon cancer, due to mutations in APC. EB1 also interacts with the plus-ends of microtubules and targets APC to microtubule tips [2-6]. Since APC is detected on the kinetochores of chromosomes, it has been hypothesized that the EB1-APC interaction connects microtubule spindles to the kinetochores and regulates microtubule stability [7-9]. In yeast, EB1 regulates microtubule dynamics [6, 10, 11], and its binding domain in APC may be conserved in Kar9, an EB1 binding protein involved in the microtubule-capturing mechanism [12-14]. These results suggest that the interaction of EB1 and APC is important and may be conserved. However, it is largely unknown whether the EB1-APC interaction affects microtubule dynamics. Here, we show that EB1 potently promotes microtubule polymerization in vitro and in permeabilized cells, but, surprisingly, only in the presence of the COOH-terminal EB1 binding domain of APC (C-APC). Significantly, this C-APC activity is abolished by phosphorylation, which also disrupts its ability to bind to EB1. Furthermore, yeast EB1 protein effectively substitutes for the human protein but also requires C-APC in promoting microtubule polymerization. Finally, C-APC is able to promote microtubule polymerization when stably expressed in APC mutant cells, demonstrating the ability of C-APC to promote microtubule assembly in vivo. Thus, the interaction between EB1 and APC plays an essential role in the regulation of microtubule polymerization, and a similar mechanism may be conserved in yeast.

Original languageEnglish
Pages (from-to)1062-1067
Number of pages6
JournalCurrent Biology
Volume11
Issue number13
DOIs
Publication statusPublished - Jul 10 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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