Efimova Nadia, Grimaldi Ashley, Bachmann Alice, Frye Keyada, Zhu Xiaodong, Feoktistov Alexander, Straube Anne, Kaverina Irina
Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville 37232, TN, USA.
Centre for Mechanochemical Cell Biology, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
J Cell Sci. 2014 Dec 15;127(Pt 24):5179-88. doi: 10.1242/jcs.149633. Epub 2014 Oct 24.
The kinesin KIF1C is known to regulate podosomes, actin-rich adhesion structures that remodel the extracellular matrix during physiological processes. Here, we show that KIF1C is a player in the podosome-inducing signaling cascade. Upon induction of podosome formation by protein kinase C (PKC), KIF1C translocation to the cell periphery intensifies and KIF1C accumulates both in the proximity of peripheral microtubules that show enrichment for the plus-tip-associated proteins CLASPs and around podosomes. Importantly, without CLASPs, both KIF1C trafficking and podosome formation are suppressed. Moreover, chimeric mitochondrially targeted CLASP2 recruits KIF1C, suggesting a transient CLASP-KIF1C association. We propose that CLASPs create preferred microtubule tracks for KIF1C to promote podosome induction downstream of PKC.
已知驱动蛋白KIF1C可调节足体，足体是富含肌动蛋白的粘附结构，在生理过程中重塑细胞外基质。在此，我们表明KIF1C是足体诱导信号级联反应中的一个参与者。在蛋白激酶C（PKC）诱导足体形成后，KIF1C向细胞周边的易位增强，并且KIF1C在显示正端相关蛋白CLASPs富集的周边微管附近以及足体周围积累。重要的是，没有CLASPs时，KIF1C的运输和足体形成均受到抑制。此外，嵌合的线粒体靶向CLASP2招募KIF1C，提示CLASP与KIF1C存在短暂关联。我们提出，CLASPs为KIF1C创建了优先的微管轨道，以促进PKC下游的足体诱导。
