KIF17 stabilizes microtubules and contributes to epithelial morphogenesis by acting at MT plus ends with EB1 and APC.

KIF17 stabilizes microtubules and contributes to epithelial morphogenesis by acting at MT plus ends with EB1 and APC.
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DOI:
10.1083/jcb.201006044
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发表时间:
2010-08-09
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Kreitzer G
Kreitzer G
中科院分区:
其他
文献类型:
--
作者:
Jaulin F;Kreitzer G

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细胞极性部分由Kif17介导的微管动力学和聚合速率调节决定。上皮极化与微管阵列的选择性稳定和重组有关。然而,上皮形态发生过程中MT稳定的上游事件和下游后果仍不清楚。我们发现,顺行驱动蛋白KIF17定位于MT加端,稳定MT,并影响上皮结构。将KIF17靶向生长中的MT的正末端需要驱动蛋白运动活性和与EB1的相互作用。反过来,KIF17参与将腺瘤性结肠息肉病(APC)定位于MT亚组的正末端。我们发现,KIF17影响MT动力学,聚合速率,和MT加上末端稳定,以产生后乙酰化的MT。在三维基质中生长的细胞中KIF17的耗尽导致异常上皮囊肿,其不能产生单个中心腔并不能产生根尖标记物。这些发现暗示KIF17在MT稳定事件中有助于上皮极化和形态发生。
Cell polarity is determined in part by Kif17-mediated regulation of microtubule dynamics and polymerization rates. Epithelial polarization is associated with selective stabilization and reorganization of microtubule (MT) arrays. However, upstream events and downstream consequences of MT stabilization during epithelial morphogenesis are still unclear. We show that the anterograde kinesin KIF17 localizes to MT plus ends, stabilizes MTs, and affects epithelial architecture. Targeting of KIF17 to plus ends of growing MTs requires kinesin motor activity and interaction with EB1. In turn, KIF17 participates in localizing adenomatous polyposis coli (APC) to the plus ends of a subset of MTs. We found that KIF17 affects MT dynamics, polymerization rates, and MT plus end stabilization to generate posttranslationally acetylated MTs. Depletion of KIF17 from cells growing in three-dimensional matrices results in aberrant epithelial cysts that fail to generate a single central lumen and to polarize apical markers. These findings implicate KIF17 in MT stabilization events that contribute to epithelial polarization and morphogenesis.
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