CHMP1 functions as a member of a newly defined family of vesicle trafficking proteins.
CHMP1 functions as a member of a newly defined family of vesicle trafficking proteins.
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DOI：
10.1242/jcs.114.13.2395
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发表时间：
2001-07
影响因子：
4
通讯作者：
T. Howard;D. Stauffer;C. Degnin;S. Hollenberg
中科院分区：
文献类型：
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作者：
T. Howard;D. Stauffer;C. Degnin;S. Hollenberg
多囊泡体是充满囊泡的内体，其将蛋白质靶向溶酶体内部。我们已经鉴定出一种保守的真核蛋白，即人 CHMP1，它与多泡体的形成密切相关。免疫细胞化学和生化分级分离将 CHMP1 定位于早期内体，并且 CHMP1 与 SKD1/VPS4 发生物理相互作用，SKD1/VPS4 是一种与酵母中的多泡体分选直接相关的高度保守的蛋白质。与突变 SKD1 蛋白的作用类似，人 CHMP1 融合衍生物的过度表达会扩张内体区室并破坏几种内体标记物的正常分布。酿酒酵母的遗传学研究进一步支持 CHMP1 在囊泡运输中的保守作用。 CHM1（CHMP1 的芽殖酵母同源物）的缺失会导致羧肽酶 S 和 Y 的分选缺陷，并产生异常的多层前液泡区室。该表型将 CHM1 归类为 E 类液泡蛋白分选基因的成员。酵母 Chm1p 属于一个结构相关但相当不同的蛋白质家族，包括 Vps24p 和 Snf7p 以及三种新蛋白质 Chm2p、Chm5p 和 Chm6p，它们对于多泡体分选都是必需的。这些观察结果表明，保守的 CHMP/Chmp 家族是一组对于理解真核生物中多囊泡体分选至关重要的蛋白质。
A multivesicular body is a vesicle-filled endosome that targets proteins to the interior of lysosomes. We have identified a conserved eukaryotic protein, human CHMP1, which is strongly implicated in multivesicular body formation. Immunocytochemistry and biochemical fractionation localize CHMP1 to early endosomes and CHMP1 physically interacts with SKD1/VPS4, a highly conserved protein directly linked to multivesicular body sorting in yeast. Similar to the action of a mutant SKD1 protein, overexpression of a fusion derivative of human CHMP1 dilates endosomal compartments and disrupts the normal distribution of several endosomal markers. Genetic studies in Saccharomyces cerevisiae further support a conserved role of CHMP1 in vesicle trafficking. Deletion of CHM1, the budding yeast homolog of CHMP1, results in defective sorting of carboxypeptidases S and Y and produces abnormal, multi-lamellar prevacuolar compartments. This phenotype classifies CHM1 as a member of the class E vacuolar protein sorting genes. Yeast Chm1p belongs to a structurally-related, but rather divergent family of proteins, including Vps24p and Snf7p and three novel proteins, Chm2p, Chm5p and Chm6p, which are all essential for multivesicular body sorting. These observations identify the conserved CHMP/Chmp family as a set of proteins fundamental to understanding multivesicular body sorting in eukaryotic organisms.