Caveolin-1 is ubiquitinated and targeted to intralumenal vesicles in endolysosomes for degradation.
Caveolin-1 is ubiquitinated and targeted to intralumenal vesicles in endolysosomes for degradation.
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DOI：
10.1083/jcb.201003086
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发表时间：
2010-11-01
期刊：
影响因子：
--
通讯作者：
Helenius A
中科院分区：
文献类型：
--
作者：
Hayer A;Stoeber M;Ritz D;Engel S;Meyer HH;Helenius A
当小窝组装受损时，小窝蛋白-1被降解的途径的鉴定表明，“小窝体”可能是等待降解的蛋白质的内体积累。小泡是由小泡蛋白、小泡和富含胆固醇的膜组成的寿命较长的质膜微域。关于小泡是如何分解的，以及它们的外壳成分是如何降解的，人们知之甚少。我们研究了CV1细胞中一种主要的小泡蛋白CAV1的降解。CAV1降解非常缓慢，但破坏小泡组装可以加速其更新。现在，CAV1在被降解的晚期内体（LE）和溶酶体中被检测到。靶向降解途径需要泛素化和运输所需的内体分选复合物（ESCRT）机制，以包含在内体的腔内囊泡中。双标签策略使我们能够监测CAV1暴露于活细胞中成熟LE个体的酸性管腔中。重要的是，我们发现“腔体”，之前被我们的团队描述为不同于核内体的独立细胞器，实际上对应于由等待降解的过表达CAV1积累修饰的晚期核内体室室。这些发现使我们对CAV1的内吞运输模型进行了修订。
Identification of the pathway by which caveolin-1 is degraded when caveolae assembly is compromised suggests that “caveosomes” may be endosomal accumulations of the protein awaiting degradation. Caveolae are long-lived plasma membrane microdomains composed of caveolins, cavins, and a cholesterol-rich membrane. Little is known about how caveolae disassemble and how their coat components are degraded. We studied the degradation of caveolin-1 (CAV1), a major caveolar protein, in CV1 cells. CAV1 was degraded very slowly, but turnover could be accelerated by compromising caveolae assembly. Now, CAV1 became detectable in late endosomes (LE) and lysosomes where it was degraded. Targeting to the degradative pathway required ubiquitination and the endosomal sorting complex required for transport (ESCRT) machinery for inclusion into intralumenal vesicles in endosomes. A dual-tag strategy allowed us to monitor exposure of CAV1 to the acidic lumen of individual, maturing LE in living cells. Importantly, we found that “caveosomes,” previously described by our group as independent organelles distinct from endosomes, actually correspond to late endosomal compartments modified by the accumulation of overexpressed CAV1 awaiting degradation. The findings led us to a revised model for endocytic trafficking of CAV1.
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DOI：
10.1083/jcb.200903053
发表时间：
2009-06-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bastiani M;Liu L;Hill MM;Jedrychowski MP;Nixon SJ;Lo HP;Abankwa D;Luetterforst R;Fernandez-Rojo M;Breen MR;Gygi SP;Vinten J;Walser PJ;North KN;Hancock JF;Pilch PF;Parton RG
通讯作者：
Parton RG
DOI：
10.1083/jcb.200407078
发表时间：
2005-01-31
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kirkham M;Fujita A;Chadda R;Nixon SJ;Kurzchalia TV;Sharma DK;Pagano RE;Hancock JF;Mayor S;Parton RG
通讯作者：
Parton RG
影响因子：
4.8
作者：
Liu, Libin;Pilch, Paul F.
通讯作者：
Pilch, Paul F.
DOI：
10.1073/pnas.172196599
发表时间：
2002-08-20
影响因子：
11.1
作者：
Fernandez, I;Ying, YS;Anderson, RGW
通讯作者：
Anderson, RGW
影响因子：
4.8
作者：
Pol, A;Lu, A;Enrich, C
通讯作者：
Enrich, C