A role for Rab5 activity in the biogenesis of endosomal and lysosomal compartments
A role for Rab5 activity in the biogenesis of endosomal and lysosomal compartments
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DOI：
10.1016/j.bbrc.2007.09.089
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发表时间：
2007-12-07
影响因子：
3.1
通讯作者：
Tanaka, Yoshitaka
中科院分区：
文献类型：
--
作者：
Hirota, Yuko;Kuronita, Toshio;Tanaka, Yoshitaka
Rab 5是一个小的GT3，在早期核内体的同型融合和细胞内囊泡运输的调节中发挥作用。我们在这里表明，GFP标记的GTP酶缺陷型Rab 5 b（Rab 5 bQ 79 L）在NRK细胞中的表达导致连续形成三种形态和功能不同类型的内体。GFP-Rab 5 bQ 79 L的表达最初引起早期内体的同型融合，伴随着TGN驻留货物分子的重新分布，随后与晚期内体/溶酶体融合，导致形成具有早期内体和晚期内体/溶酶体特征的巨大杂合细胞器。令人惊讶的是，巨大的内体逐渐破碎和收缩，导致早期内体簇的积累和晚期内体/溶酶体的同时重组，这一过程通过用磷脂酰肌醇-3-激酶（PI（3）K）抑制剂处理而加速。渥曼青霉素我们假设，这样的顺序过程反映了后期内体/溶酶体的生物发生和维持，大概是通过与早期内体的直接融合和随后的杂交细胞器的裂变。因此，我们的研究结果表明Rab 5不仅在早期内吞途径中，而且在晚期内吞途径中，与PI（3）K活性协调的膜运输中起调节作用。(C)2007爱思唯尔公司All rights reserved.
Rab5 is a small GTPase that plays roles in the homotypic fusion of early endosomes and regulation of intracellular vesicle transport. We show here that expression of GFP-tagged GTPase-deficient form of Rab5b (Rab5bQ79L) in NRK cells results in the sequential formation of three morphologically and functionally distinct types of endosomes. Expression of GFP-Rab5bQ79L initially caused a homotypic fusion of early endosomes accompanying a redistribution of the TGN-resident cargo molecules, and subsequent fusion with late endosomes/lysosomes, leading to the formation of giant hybrid organelles with features of early endosomes and late endosomes/lysosomes. Surprisingly, the giant endosomes gradually fragmented and shrunk, leading to the accumulation of early endosome clusters and concurrent reformation of late endosomes/lysosomes, a process accelerated by treatment with a phosphatidylinositol-3-kinase (PI(3)K) inhibitor. wortmannin. We postulate that such sequential processes reflect the biogenesis and maintenance of late endosomes/lysosomes, presumably via direct fusion with early endosomes and subsequent fission from hybrid organelles. Thus, our findings suggest a regulatory role for Rab5 in not only the early endocytic pathway, but also the late endocytic pathway, of membrane trafficking in coordination with PI(3)K activity. (C) 2007 Elsevier Inc. All rights reserved.