Termination of isoform-selective Vps21/Rab5 signaling at endolysosomal organelles by Msb3/Gyp3.
Termination of isoform-selective Vps21/Rab5 signaling at endolysosomal organelles by Msb3/Gyp3.
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DOI：
10.1111/j.1600-0854.2012.01390.x
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发表时间：
2012-10
期刊：
影响因子：
--
通讯作者：
Merz AJ
中科院分区：
文献类型：
--
作者：
Nickerson DP;Russell MRG;Lo SY;Chapin HC;Milnes J;Merz AJ
通过内切体和溶酶体的运输由Rab5和Rab7家族的小G蛋白控制。和人类一样，酿酒酵母有三个Rab5(Vps21、Ypt52和Ypt53)和一个Rab7(Ypt7)。在这里，我们阐明了酵母Rab5s的功能和调控。利用绿色荧光蛋白标记的货物，一种新的定量多泡体分选方法，以及电子显微镜，我们发现在vps 21ΔPYT52Δ双突变体中，多囊小体的生物发生和货物分选受到严重损害。Ypt53是Rab5的第三个类似蛋白，在正常生长过程中几乎不表达，但它的转录在细胞应激下通过钙调神经磷酸酶-Crz1途径强烈诱导。在胁迫耐受性中对Rab5活性的要求有助于确定Msb3/Gyp3是主要的Rab5 GAP(GTP酶加速蛋白)，体外GAP分析证实Vps21是Gyp3的首选靶标。最后，我们证明了Gyp3通过阻止Vps21在溶酶体空泡上的积聚，在空间上将活性的Vps21限制在中间的内体隔室。因此，Gyp3作为隔室绝缘体，加强内溶酶体途径的倒数第二个和末端隔间的边界。
Traffic through endosomes and lysosomes is controlled by small G-proteins of the Rab5 and Rab7 families. Like humans, Saccharomyces cerevisiae has three Rab5s (Vps21, Ypt52, and Ypt53), and one Rab7 (Ypt7). Here, we elucidate the functional roles and regulation of the yeast Rab5s. Using GFP-tagged cargoes, a novel quantitative multivesicular body (MVB) sorting assay, and electron microscopy, we show that MVB biogenesis and cargo sorting are severely impaired in vps21Δ ypt52Δ double mutants. Ypt53, the third Rab5 paralog, is hardly expressed during normal growth but its transcription is strongly induced by cellular stress through the calcineurin-Crz1 pathway. The requirement for Rab5 activity in stress tolerance facilitated identification of Msb3/Gyp3 as the principal Rab5 GAP (GTPase accelerating protein), and in vitro GAP assays verified that Vps21 is a preferred Gyp3 target. Finally, we demonstrate that Gyp3 spatially restricts active Vps21 to intermediate endosomal compartments by preventing Vps21 accumulation on lysosomal vacuoles. Gyp3 therefore operates as a compartmental insulator that enforces the boundary between penultimate and terminal compartments of the endolysosomal pathway.
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DOI：
10.1083/jcb.200508166
发表时间：
2006-02-27
期刊：
The Journal of cell biology
影响因子：
--
作者：
Azmi I;Davies B;Dimaano C;Payne J;Eckert D;Babst M;Katzmann DJ
通讯作者：
Katzmann DJ
DOI：
10.1038/nrm2937
发表时间：
2010-08
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
7.8
作者：
Brett, Christopher L.;Plemel, Rachael L.;Lobinger, Braden T.;Vignali, Marissa;Fields, Stanley;Merz, Alexey J.
通讯作者：
Merz, Alexey J.
影响因子：
4.8
作者：
Albert, S;Gallwitz, D
通讯作者：
Gallwitz, D
影响因子：
3.3
作者：
Gerrard, SR;Bryant, NJ;Stevens, TH
通讯作者：
Stevens, TH