Kobayashi N, Reiser J, Kriz W, Kuriyama R, Mundel P
Department of Anatomy and Cell Biology, University of Heidelberg, D-69120 Heidelberg, Germany.
J Cell Biol. 1998 Dec 28;143(7):1961-70. doi: 10.1083/jcb.143.7.1961.
Podocytes are unique cells that are decisively involved in glomerular filtration. They are equipped with a complex process system consisting of major processes and foot processes whose function is insufficiently understood (Mundel, P., and W. Kriz. 1995. Anat. Embryol. 192:385-397). The major processes of podocytes contain a microtubular cytoskeleton. Taking advantage of a recently established cell culture system for podocytes with preserved ability to form processes (Mundel, P., J. Reiser, A. Zúñiga Mejía Borja, H. Pavenstädt, G.R. Davidson, W. Kriz, and R. Zeller. 1997b. Exp. Cell Res. 36:248-258), we studied the functional significance of the microtubular system in major processes. The following data were obtained: (a) Microtubules (MTs) in podocytes show a nonuniform polarity as revealed by hook-decoration. (b) CHO1/ MKLP1, a kinesin-like motor protein, is associated with MTs in podocytes. (c) Treatment of differentiating podocytes with CHO1/MKLP1 antisense oligonucleotides abolished the formation of processes and the nonuniform polarity of MTs. (d) During the recovery from taxol treatment, taxol-stabilized (nocodazole- resistant) MT fragments were distributed in the cell periphery along newly assembled nocodazole-sensitive MTs. A similar distribution pattern of CHO1/MKLP1 was found under these circumstances, indicating its association with MTs. (e) In the recovery phase after complete depolymerization, MTs reassembled exclusively at centrosomes. Taken together, these findings lead to the conclusion that the nonuniform MT polarity in podocytes established by CHO1/MKLP1 is necessary for process formation.
足细胞是肾小球滤过过程中起关键作用的独特细胞。它们具有由主突和足突组成的复杂突起系统，但其功能尚不完全清楚（Mundel, P., and W. Kriz. 1995. Anat. Embryol. 192:385 - 397）。足细胞的主突含有微管细胞骨架。利用最近建立的具有保留突起形成能力的足细胞培养系统（Mundel, P., J. Reiser, A. Zúñiga Mejía Borja, H. Pavenstädt, G.R. Davidson, W. Kriz, and R. Zeller. 1997b. Exp. Cell Res. 36:248 - 258），我们研究了主突中微管系统的功能意义。获得了以下数据：（a）足细胞中的微管（MTs）通过钩状标记显示出不均匀的极性。（b）CHO1/MKLP1，一种类驱动蛋白，与足细胞中的MTs相关联。（c）用CHO1/MKLP1反义寡核苷酸处理分化中的足细胞可消除突起的形成和MTs的不均匀极性。（d）在从紫杉醇处理中恢复的过程中，紫杉醇稳定的（抗诺考达唑的）MT片段沿着新组装的对诺考达唑敏感的MTs分布在细胞周边。在这些情况下发现了CHO1/MKLP1的类似分布模式，表明其与MTs相关联。（e）在完全解聚后的恢复阶段，MTs仅在中心体重新组装。综上所述，这些发现得出结论，由CHO1/MKLP1建立的足细胞中MTs的不均匀极性对于突起形成是必要的。
