Organelle-specific control of intracellular transport: Distinctly targeted isoforms of the regulator Klar
Organelle-specific control of intracellular transport: Distinctly targeted isoforms of the regulator Klar
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DOI：
10.1091/mbc.e04-10-0920
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发表时间：
2005-03-01
影响因子：
3.3
通讯作者：
Welte, MA
中科院分区：
文献类型：
--
作者：
Guo, Y;Jangi, S;Welte, MA
细胞中基于微管的运输由一小组不同的马达提供动力，但运输的时间和目的地可以以货物特异性的方式控制。这种特异性的机制基础尚不清楚。为了解决这个问题，我们分析了果蝇Klarsicht（Klar）蛋白，调节不同的微管为基础的运输过程。我们发现，本地化的Klar其货物是至关重要的Klar功能。使用突变，我们确定功能重要的区域Klar赋予不同的货物特异性。在卵巢中，Klar存在于核膜上，这需要C-末端KASH结构域的定位。在早期胚胎中，Klar附着在脂滴上，这是一种由可变剪接外显子编码的新型C末端结构域介导的定位。在培养的细胞中，这两个结构域足以靶向正确的细胞内位置。我们的分析解开Klar的模块化组织：我们提出，一个核心区域的电机调节不可或缺的是连接到可变域，使细胞可以针对监管机构重叠，但不同的功能，以特定的货物。这种异构体变异可能是一种通用策略，用于调整共同的调节机制，以特异性地控制多个细胞器的运动和定位。
Microtubule-based transport in cells is powered by a small set of distinct motors, yet timing and destination of transport can be controlled in a cargo-specific manner. The mechanistic basis for this specificity is not understood. To address this question, we analyzed the Drosophila Klarsicht (Klar) protein that regulates distinct microtubule-based transport processes. We find that localization of Klar to its cargoes is crucial for Klar function. Using mutations, we identify functionally important regions of Klar that confer distinct cargo specificity. In ovaries, Klar is present on the nuclear envelope, a localization that requires the C-terminal KASH domain. In early embryos, Klar is attached to lipid droplets, a localization mediated by a novel C-terminal domain encoded by an alternatively spliced exon. In cultured cells, these two domains are sufficient for targeting to the correct intracellular location. Our analysis disentangles Klar's modular organization: we propose that a core region integral to motor regulation is attached to variable domains so that the cell can target regulators with overlapping, yet distinct functions to specific cargoes. Such isoform variation may be a general strategy for adapting a common regulatory mechanism to specifically control motion and positioning of multiple organelles.