Different steady state subcellular distributions of the three splice variants of lysosome-associated membrane protein LAMP-2 are determined largely by the COOH-terminal amino acid residue.
Different steady state subcellular distributions of the three splice variants of lysosome-associated membrane protein LAMP-2 are determined largely by the COOH-terminal amino acid residue.
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DOI：
10.1083/jcb.137.5.1161
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发表时间：
1997-06-02
期刊：
影响因子：
--
通讯作者：
Fambrough DM
中科院分区：
文献类型：
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作者：
Gough NR;Fambrough DM
广泛糖基化的溶酶体相关膜蛋白(LAMP)-2a、b和c是由一个基因通过选择性剪接产生的，该基因在跨膜区和胞浆区产生不同的蛋白质。溶酶体靶向信号位于这些蛋白质的胞浆结构域中。LAMP并不局限于溶酶体，也可以在内体和细胞表面发现。我们研究了由禽类LAMP-1的腔结构域和禽类LAMP-2的选择性剪接结构域组成的嵌合体的亚细胞分布。含有LAMP-2c胞浆结构域的嵌合体主要表现为溶酶体分布，而含有LAMP-2a或b胞浆结构域的嵌合体在细胞表面存在较高水平的嵌合体。细胞表面表达的增加是由于靶向信号识别的差异，而不是细胞内转运机制的饱和。定点突变定义了胞液尾部的COOH末端残基在控制LAMP-2a、b和c在细胞内隔间和细胞表面之间的分布方面起关键作用。
The extensively glycosylated lysosome-associated membrane proteins (LAMP)-2a, b, and c are derived from a single gene by alternative splicing that produces proteins with differences in the transmembrane and cytosolic domains. The lysosomal targeting signals reside in the cytosolic domain of these proteins. LAMPs are not restricted to lysosomes but can also be found in endosomes and at the cell surface. We investigated the subcellular distribution of chimeras comprised of the lumenal domain of avian LAMP-1 and the alternatively spliced domains of avian LAMP-2. Chimeras with the LAMP-2c cytosolic domain showed predominantly lysosomal distribution, while higher levels of chimeras with the LAMP-2a or b cytosolic domain were present at the cell surface. The increase in cell surface expression was due to differences in the recognition of the targeting signals and not saturation of intracellular trafficking machinery. Site-directed mutagenesis defined the COOH-terminal residue of the cytosolic tail as critical in governing the distributions of LAMP-2a, b, and c between intracellular compartments and the cell surface.