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Mol Biol Cell August 1, 2014; 25 (15): 2272-81.

Kinetochore-microtubule attachment throughout mitosis potentiated by the elongated stalk of the kinetochore kinesin CENP-E.

Vitre B , Gudimchuk N , Borda R , Kim Y , Heuser JE , Cleveland DW , Grishchuk EL .

Centromere protein E (CENP-E) is a highly elongated kinesin that transports pole-proximal chromosomes during congression in prometaphase. During metaphase, it facilitates kinetochore-microtubule end-on attachment required to achieve and maintain chromosome alignment. In vitro CENP-E can walk processively along microtubule tracks and follow both growing and shrinking microtubule plus ends. Neither the CENP-E-dependent transport along microtubules nor its tip-tracking activity requires the unusually long coiled-coil stalk of CENP-E. The biological role for the CENP-E stalk has now been identified through creation of "Bonsai" CENP-E with significantly shortened stalk but wild-type motor and tail domains. We demonstrate that Bonsai CENP-E fails to bind microtubules in vitro unless a cargo is contemporaneously bound via its C-terminal tail. In contrast, both full-length and truncated CENP-E that has no stalk and tail exhibit robust motility with and without cargo binding, highlighting the importance of CENP-E stalk for its activity. Correspondingly, kinetochore attachment to microtubule ends is shown to be disrupted in cells whose CENP-E has a shortened stalk, thereby producing chromosome misalignment in metaphase and lagging chromosomes during anaphase. Together these findings establish an unexpected role of CENP-E elongated stalk in ensuring stability of kinetochore-microtubule attachments during chromosome congression and segregation.

PubMed ID: 24920822
PMC ID: PMC4116301
Article link: Mol Biol Cell
Grant support: [+]
Genes referenced: bub1b cenpe dld dnai1 myc noct picalml

Article Images: [+] show captions
References [+] :
Abrieu, CENP-E as an essential component of the mitotic checkpoint in vitro. 2000, Pubmed, Xenbase

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