Altered trafficking and turnover of LAMP-1 in Pompe disease-affected cells.
Altered trafficking and turnover of LAMP-1 in Pompe disease-affected cells.
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庞贝病影响细胞中 LAMP-1 的运输和更新发生改变。
DOI：
10.1006/mgme.1998.2800
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发表时间：
1999
影响因子：
3.8
通讯作者：
D. Brooks
中科院分区：
文献类型：
--
作者：
P. Meikle;M. Yan;E. M. Ravenscroft;E. L. Isaac;J. Hopwood;D. Brooks
溶酶体相关膜蛋白（LAMP-1）在受溶酶体贮积症影响的个体的细胞和血浆中升高;然而，这种升高的机制尚未明确。在这项研究中，我们调查了LAMP-1的合成，糖加工，运输和营业额在人类皮肤成纤维细胞从庞贝氏症患者和对照个体。在两种细胞类型中有相似水平的LAMP-1合成，但与对照（T1/2 = 17 min）成纤维细胞相比，庞贝氏症（T1/2 = 25 min）中的糖加工被延迟。与对照（T1/2 = 100 min）细胞相比，LAMP-1向庞贝氏菌溶酶体的运输也有明显延迟（T1/2 = 200 min）。一部分新合成的LAMP-1（庞贝氏症中为5.4%，对照组中为8.5%）被运输出细胞（对照组中T1/2 = 3.5 h），尽管明显小于溶酶体形式，但仍具有跨膜结构域和胞质尾区。相反，LAMP-1的可溶性溶酶体池没有尾序列，表明它已从膜上被剪切下来。在周转研究中，与对照组（T1/2 = 1. 6天）的细胞，这意味着在庞贝氏症细胞中蛋白水解或溶酶体功能降低。这些结果表明改变交通和周转的LAMP-1在存储障碍，并确定不同的细胞内和细胞外池的可溶性LAMP-1，表明替代的运输途径。
The lysosome-associated membrane protein (LAMP-1) is elevated in the cells and plasma from lysosomal storage disorder-affected individuals; however, the mechanism of this elevation is not well defined. In this study we have investigated the synthesis, glycoprocessing, trafficking, and turnover of LAMP-1 in human skin fibroblasts from Pompe disease patients and control individuals. There were similar levels of LAMP-1 synthesis in both cell types, but glycoprocessing was retarded in Pompe (T1/2 = 25 min) compared to control (T1/2 = 17 min) fibroblasts. There was also a marked delay in trafficking of LAMP-1 to lysosomes of Pompe (T1/2 = 200 min) compared to control (T1/2 = 100 min) cells. A proportion of newly synthesized LAMP-1 (5.4% in Pompe and 8.5% in controls) was trafficked out of the cell (T1/2 = 3.5 h in controls) and, although significantly smaller than the lysosomal form, still had a transmembrane domain and cytoplasmic tail. In contrast, a soluble lysosomal pool of LAMP-1 had no tail sequence, suggesting that it had been clipped from the membrane. In turnover studies, LAMP-1 was more stable in Pompe (T1/2 = 4.9 days) compared to control (T1/2 = 1. 6 days) cells, implying either reduced proteolysis or lysosomal function, in Pompe cells. These results indicate altered traffic and turnover of LAMP-1 in storage disorders and identify different intracellular and extracellular pools of soluble LAMP-1, suggesting alternative trafficking pathways.
DOI：
10.1016/s0021-9258(18)31488-1
发表时间：
1993-04
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
R. Sawada;K. Jardine;M. Fukuda
通讯作者：
R. Sawada;K. Jardine;M. Fukuda
编码人溶酶体膜糖蛋白 h-lamp-1 和 h-lamp-2 的 cDNA 的克隆。
DOI：
--
发表时间：
1988
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Fukuda,M;Viitala,J;Matteson,J;Carlsson,SR
通讯作者：
Carlsson,SR