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First published online April 3, 2008
doi: 10.1242/10.1242/jcs.018176

Journal of Cell Science 121, 1334-1343 (2008)
Published by The Company of Biologists 2008
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Research Article

Centrosome separation driven by actin-microfilaments during mitosis is mediated by centrosome-associated tyrosine-phosphorylated cortactin

Wenqi Wang*, Luyun Chen*, Yubo Ding, Jing Jin and Kan Liao{ddagger}

State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, People's Republic of China

{ddagger} Author for correspondence (e-mail: kliao{at}sibs.ac.cn)

Accepted 31 January 2008

The regulation of protein tyrosine phosphorylation is an important aspect during the cell cycle. From G2-M transition to mitotic anaphase, phosphorylation of Tyr421, Tyr466 and Tyr482 of cortactin, an actin-filament associated protein, is dramatically induced. The phosphorylated cortactin is almost exclusively associated with centrosomes or spindle poles during mitosis. At G2-M transition prior to the breakdown of the nuclear envelope, two duplicated centrosomes migrate towards opposite ends of the nucleus to form the spindle poles. This centrosome-separation process and also the start of mitosis are inhibited or delayed by the depolymerization of actin filaments. Also inhibited is the separation of centrosomes when a truncated form of cortactin is expressed, whose C-terminus contains the tyrosine phosphorylation region but lacks the actin-binding domains. We introduced mutations at the tyrosine phosphorylation sites in the truncated C-terminus of cortactin and found that the C-terminus could no longer interfere with centrosome separation process. Our study shows that, cortactin phosphorylated at Tyr421, Tyr466 and Tyr482 mediates the actin-filament-driven centrosome separation at G2-M transition by providing a bridge between the centrosome and actin-filaments.

Key words: Cortactin, Cortactin tyrosine phosphorylation, Centrosome separation, Actin-filament, Focal adhesion points, Src kinase






© The Company of Biologists Ltd 2008