Dynein-dependent Movement of Autophagosomes Mediates Efficient Encounters with Lysosomes
Dynein-dependent Movement of Autophagosomes Mediates Efficient Encounters with Lysosomes
复制标题
DOI：
10.1247/csf.08005
复制
发表时间：
2008-01-01
影响因子：
1.5
通讯作者：
Yoshimori, Tamotsu
中科院分区：
文献类型：
--
作者：
Kimura, Shunsuke;Noda, Takeshi;Yoshimori, Tamotsu
自噬是一种携带细胞质成分到溶酶体降解的膜运输途径。在此过程中，自噬体（一种双膜细胞器）重新生成，将细胞质蛋白质和细胞器隔离，并将其传递给溶酶体。然而，自噬体靶向溶酶体的机制尚未确定。在这里，我们观察了定位于自噬体的微管相关蛋白轻链3 （LC3）的实时行为，并表明自噬体以微管和动力蛋白-动力蛋白运动复合物依赖的方式运动。自噬体形成后，向中心体方向快速矢量运动，溶酶体通常集中于中心体。微量注射抗LC3抗体可抑制这种运动；此外，通过FRAP，我们发现抗lc3抗体注射导致自噬体靶向溶酶体的缺陷。总的来说，我们的数据证明了自噬体运动的功能意义，它能够从细胞质有效地传递到溶酶体。
Autophagy is a membrane trafficking pathway that carries cytosolic components to the lysosome for degradation. During this process, the autophagosome, a double-membraned organelle, is generated de novo, sequesters cytoplasmic proteins and organelles, and delivers them to lysosomes. However, the mechanism by which autophagosomes are targeted to lysosomes has not been determined. Here, we observed the real-time behavior of microtubule-associated protein light chain 3 (LC3), which localizes to autophagosomes, and showed that autophagosomes move in a microtubule- and dynein-dynactin motor complex-dependent manner. After formation, autophagosomes show a rapid vectorial movement in the direction of the centrosome, where lysosomes are usually concentrated. Microinjection of antibodies against LC3 inhibited this movement; furthermore, using FRAP, we showed that anti-LC3 antibody injection caused a defect in targeting of autophagosomes to lysosomes. Collectively, our data demonstrate the functional significance of autophagosome movement that enables effective delivery from the cytosol to lysosomes.