Clonal tests of conventional kinesin function during cell proliferation and differentiation
Clonal tests of conventional kinesin function during cell proliferation and differentiation
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DOI：
10.1091/mbc.11.4.1329
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发表时间：
2000-04-01
影响因子：
3.3
通讯作者：
Saxton, WM
中科院分区：
文献类型：
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作者：
Brendza, RP;Sheehan, KB;Saxton, WM
果蝇驱动蛋白重链基因（Khc）的无效突变在幼虫第二龄期间是致命的，这表明传统驱动蛋白对于神经元中的快速轴突运输至关重要，但其在其他地方的功能尚不确定。为了测试其他组织，通过有丝分裂重组使幼虫中的单个成虫细胞对 Khc 无效。令人惊讶的是，无效细胞产生了成体组织的大克隆。细胞增殖率没有降低，表明常规驱动蛋白对于细胞生长或分裂不是必需的。这表明在未分化细胞中，囊泡从高尔基体转运到内质网或质膜可以在没有常规驱动蛋白的情况下以正常速率进行。在无效创始人细胞产生的成体眼克隆中，存在一些分化缺陷，导致轻微的超微结构变化，但与内质网、线粒体或囊泡的定位或运输方面的严重问题不一致。相比之下，高度拉长的 Khc null 鬃毛轴导致的有缺陷的角质层沉积表明，传统驱动蛋白对于某些细胞类型（特别是那些必须构建和维持长细胞质延伸的细胞）中正确的分泌囊泡运输至关重要。驱动蛋白重链的普遍存在性和进化保守性证明其在所有细胞中都具有功能。我们认为间期细胞器远离细胞中心的运动是由多层运输机制驱动的；也就是说，单个细胞器可以使用驱动蛋白相关蛋白和肌球蛋白，以及传统的驱动蛋白，向细胞外围移动。在这种情况下，除了具有极长运输轨道的细胞外，其他马达可以补偿传统驱动蛋白的损失。
Null mutations in the Drosophila Kinesin heavy chain gene (Khc), which are lethal during the second larval instar, have shown that conventional kinesin is critical for fast axonal transport in neurons, but its functions elsewhere are uncertain. To test other tissues, single imaginal cells in young larvae were rendered null for Khc by mitotic recombination. Surprisingly, the null cells produced large clones of adult tissue. The rates of cell proliferation were not reduced, indicating that conventional kinesin is not essential for cell growth or division. This suggests that in undifferentiated cells vesicle transport from the Golgi to either the endoplasmic reticulum or the plasma membrane can proceed at normal rates without conventional kinesin. In adult eye clones produced by null founder cells, there were some defects in differentiation that caused mild ultrastructural changes, but they were not consistent with serious problems in the positioning or transport of endoplasmic reticulum, mitochondria, or vesicles. In contrast, defective cuticle deposition by highly elongated Khc null bristle shafts suggests that conventional kinesin is critical for proper secretory vesicle transport in some cell types, particularly ones that must build and maintain long cytoplasmic extensions. The ubiquity and evolutionary conservation of kinesin heavy chain argue for functions in all cells. We suggest interphase organelle movements away from the cell center are driven by multilayered transport mechanisms; that is, individual organelles can use kinesin-related proteins and myosins, as well as conventional kinesin, to move toward the cell periphery. In this case, other motors can compensate for the loss of conventional kinesin except in cells that have extremely long transport tracks.