Involvement of vps33a in the fusion of uroplakin-degrading multivesicular bodies with lysosomes.
Involvement of vps33a in the fusion of uroplakin-degrading multivesicular bodies with lysosomes.
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DOI：
10.1111/j.1600-0854.2009.00950.x
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发表时间：
2009-09
期刊：
影响因子：
--
通讯作者：
Kreibich G
中科院分区：
文献类型：
--
作者：
Guo X;Tu L;Gumper I;Plesken H;Novak EK;Chintala S;Swank RT;Pastores G;Torres P;Izumi T;Sun TT;Sabatini DD;Kreibich G
终末分化的小鼠膀胱尿路上皮细胞的顶面主要由尿路上皮斑块覆盖，由六边形包装的16-nm尿斑蛋白颗粒组成。这些空斑通过梭形囊泡（FV）递送到细胞表面，梭形囊泡是最丰富的细胞质细胞器。我们已经分析了几种蛋白质在尿斑蛋白的顶端递送和内吞降解中的功能参与。虽然FV具有酸化的内腔，并且已知定位于这些细胞器的Rab 27 b参与溶酶体相关细胞器（LRO）的靶向，但FV是CD 63阴性的，因此不是典型的LRO。Vps 33 a是一种Sec 1相关蛋白，在囊泡转运至溶酶体区室中发挥作用。由于黑素体和血小板运输异常，小鼠Vps 33 a（Buff小鼠）中的点突变导致白化病和出血（Hermansky-Pudlak综合征）。这些Buff小鼠表现出在尿路上皮伞细胞中观察到的新表型，其中尿斑蛋白递送FV几乎完全被参与尿斑蛋白降解的Rab 27 b阴性多泡体（MVB）取代。MVB蓄积导致尿斑蛋白、溶酶体相关膜蛋白（LAMP）-1/2的量以及β-氨基己糖苷酶和β-葡糖脑苷脂酶的活性增加。这些结果表明，FV可以被认为是专门的分泌颗粒，将尿斑蛋白的晶体阵列递送到细胞表面，并且Vps 33 a突变干扰MVB与成熟溶酶体的融合，从而阻断尿斑蛋白降解。
The apical surface of the terminally differentiated mouse bladder urothelium is largely covered by urothelial plaques, consisting of hexagonally packed 16-nm uroplakin particles. These plaques are delivered to the cell surface by fusiform vesicles (FVs) that are the most abundant cytoplasmic organelles. We have analyzed the functional involvement of several proteins in the apical delivery and endocytic degradation of uroplakin proteins. Although FVs have an acidified lumen and Rab27b, which localizes to these organelles, is known to be involved in the targeting of lysosome-related organelles (LROs), FVs are CD63 negative and are therefore not typical LROs. Vps33a is a Sec1-related protein that plays a role in vesicular transport to the lysosomal compartment. A point mutation in mouse Vps33a (Buff mouse) causes albinism and bleeding (Hermansky-Pudlak syndrome) because of abnormalities in the trafficking of melanosomes and platelets. These Buff mice showed a novel phenotype observed in urothelial umbrella cells, where the uroplakin-delivering FVs were almost completely replaced by Rab27b-negative multivesicular bodies (MVBs) involved in uroplakin degradation. MVB accumulation leads to an increase in the amounts of uroplakins, Lysosomal-associated membrane protein (LAMP)-1/2, and the activities of β-hexosaminidase and β-glucocerebrosidase. These results suggest that FVs can be regarded as specialized secretory granules that deliver crystalline arrays of uroplakins to the cell surface, and that the Vps33a mutation interferes with the fusion of MVBs with mature lysosomes thus blocking uroplakin degradation.
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影响因子：
3.3
作者：
Gomi, Hiroshi;Mori, Kenichi;Izumi, Tetsuro
通讯作者：
Izumi, Tetsuro
影响因子：
3.3
作者：
Hu, CCA;Liang, FX;Sun, TT
通讯作者：
Sun, TT
影响因子：
--
作者：
AMANO, O;KATAOKA, S;YAMAMOTO, TY
通讯作者：
YAMAMOTO, TY
影响因子：
15.9
作者：
Barral, DC;Ramalho, JS;Seabra, MC
通讯作者：
Seabra, MC
影响因子：
4.8
作者：
Fukuda, M;Kuroda, TS;Mikoshiba, K
通讯作者：
Mikoshiba, K