Two di-leucine motifs regulate trafficking of mucolipin-1 to lysosomes.
Two di-leucine motifs regulate trafficking of mucolipin-1 to lysosomes.
复制标题
DOI：
10.1111/j.1600-0854.2006.00387.x
复制
发表时间：
2006-03
期刊：
影响因子：
--
通讯作者：
Puertollano R
中科院分区：
文献类型：
--
作者：
Vergarajauregui S;Puertollano R
粘脂蛋白-1基因的突变与IV型粘脂沉积症有关，IV型粘脂沉积症是一种以严重的神经系统和眼科异常为特征的溶酶体贮积症。Mucolipin-1是一种膜蛋白，含有6个假定的跨膜结构域，其N-和C-末端均面向胞质溶胶定位。为了获得介导这种蛋白质运输到溶酶体的分选基序的信息，我们已经产生了嵌合体，其中粘磷脂-1的N-和C-末端尾部与报告基因融合。在这篇文章中，我们报告了两个独立的双亮氨酸型图案的合作，以调节运输的粘脂-1到溶酶体的鉴定。一个双亮氨酸基序位于N-末端胞质尾部并介导直接转运至溶酶体，而另一个双亮氨酸基序位于C-末端尾部并用作衔接蛋白2依赖性内化基序。我们还发现，粘脂-1的C-末端尾部是棕榈酰化的，这种修饰可能调节内吞作用的效率。最后，两个二亮氨酸基序的诱变废除溶酶体积累，并导致在细胞表面重新分布的粘脂-1。两者合计，这些结果揭示了新的信息的图案，调节粘脂-1贩运，并建议棕榈酰化在蛋白质分选的作用。
Mutations in the mucolipin-1 gene have been linked to mucolipidosis type IV, a lysosomal storage disorder characterized by severe neurological and ophthalmologic abnormalities. Mucolipin-1 is a membrane protein containing six putative transmembrane domains with both its N- and C-termini localized facing the cytosol. To gain information on the sorting motifs that mediate the trafficking of this protein to lysosomes, we have generated chimeras in which the N- and C- terminal tail portions of mucolipin-1 were fused to a reporter gene. In this article, we report the identification of two separate di-leucine-type motifs that co-operate to regulate the transport of mucolipin-1 to lysosomes. One di-leucine motif is positioned at the N-terminal cytosolic tail and mediates direct transport to lysosomes, whereas the other di-leucine motif is found at the C-terminal tail and functions as an adaptor protein 2-dependent internalization motif. We have also found that the C-terminal tail of mucolipin-1 is palmitoylated and that this modification might regulate the efficiency of endocytosis. Finally, the mutagenesis of both di-leucine motifs abrogated lysosomal accumulation and resulted in cell-surface redistribution of mucolipin-1. Taken together, these results reveal novel information regarding the motifs that regulate mucolipin-1 trafficking and suggest a role for palmitoylation in protein sorting.
登录
查看更多内容
影响因子：
--
作者：
Munshi, UM;Clouser, CL;Menon, KMJ
通讯作者：
Menon, KMJ
DOI：
10.1083/jcb.131.2.351
发表时间：
1995-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Marks MS;Roche PA;van Donselaar E;Woodruff L;Peters PJ;Bonifacino JS
通讯作者：
Bonifacino JS
影响因子：
3.9
作者：
Bargal, R;Avidan, N;Bach, G
通讯作者：
Bach, G
影响因子：
3.5
作者：
Manzoni, M;Monti, E;Borsani, G
通讯作者：
Borsani, G
DOI：
10.1097/00005072-199503000-00002
发表时间：
1995-03-01
影响因子：
3.2
作者：
FOLKERTH, RD;ALROY, J;KOLODNY, EH
通讯作者：
KOLODNY, EH