Department of Nephrology, University Hospital, Freiburg, Germany.
PLoS One. 2013 May 1;8(5):e62165. doi: 10.1371/journal.pone.0062165. Print 2013.
The microtubular motor Kinesin-2 and its subunit Kif3a are essential for the formation of primary cilia, an organelle implicated in a wide spectrum of developmental abnormalities. Outside cilia, Kinesin-2 mediated transport has been implicated in vesicle and N-cadherin transport, but it is unknown if and how extraciliary Kif3a affects basic cellular functions such as migration or the formation of multicellular structures. Here we show that tetracycline inducible depletion of Kif3a in MDCK cells slows epithelial cell migration. Microtubules at the leading edge of Kif3a depleted cells failed to grow perpendicularly into the leading edge and microtubular dynamics were dampened in Kif3a depleted cells. Loss of Kif3a retarded lateral membrane specification and completely prevented the formation of three-dimensional spheres in collagen. These data uncover that Kif3a regulates the microtubular cytoskeleton in the cell periphery and imply that extra-ciliary Kif3a has an unexpected function in morphogenesis.
微管马达 Kinesin-2 及其亚基 Kif3a 对于初级纤毛的形成至关重要，初级纤毛是一种与广泛的发育异常有关的细胞器。在纤毛外，Kinesin-2 介导的运输已被牵连到囊泡和 N-钙黏蛋白的运输中，但尚不清楚细胞外的 Kif3a 是否以及如何影响细胞的基本功能，如迁移或多细胞结构的形成。在这里，我们表明，MDCK 细胞中 tetracycline 诱导的 Kif3a 缺失会减缓上皮细胞的迁移。Kif3a 缺失细胞的前缘微管未能垂直生长到前缘，微管动力学在 Kif3a 缺失细胞中受到抑制。Kif3a 的缺失会延迟侧膜的特化，并完全阻止三维球体在胶原中的形成。这些数据揭示了 Kif3a 调节细胞外周的微管细胞骨架，并暗示细胞外的 Kif3a 在形态发生中具有意想不到的功能。
