Department of Pathology, School of Medicine, University of Utah, Salt Lake City, UT 84132, USA.
Traffic. 2012 Jan;13(1):108-19. doi: 10.1111/j.1600-0854.2011.01300.x. Epub 2011 Nov 9.
Chediak-Higashi syndrome is an autosomal recessive disorder that affects vesicle morphology. The Chs1/Lyst protein is a member of the BEige And CHediak family of proteins. The absence of Chs1/Lyst gives rise to enlarged lysosomes. Lysosome size is regulated by a balance between vesicle fusion and fission and can be reversibly altered by acidifying the cytoplasm using Acetate Ringer's or by incubating with the drug vacuolin-1. We took advantage of these procedures to determine rates of lysosome fusion and fission in the presence or absence of Chs1/Lyst. Here, we show by microscopy, flow cytometry and in vitro fusion that the absence of the Chs1/Lyst protein does not increase the rate of lysosome fusion. Rather, our data indicate that loss of this protein decreases the rate of lysosome fission. We further show that overexpression of the Chs1/Lyst protein gives rise to a faster rate of lysosome fission. These results indicate that Chs1/Lyst regulates lysosome size by affecting fission.
Chediak-Higashi 综合征是一种常染色体隐性疾病，影响囊泡形态。Chs1/Lyst 蛋白是 BEige 和 Chediak 家族蛋白的成员。Chs1/Lyst 的缺失会导致溶酶体增大。溶酶体的大小受囊泡融合和裂变之间的平衡调节，可以通过使用乙酸盐林格氏液或用 vacuolin-1 孵育使细胞质酸化来可逆地改变。我们利用这些程序来确定在存在或不存在 Chs1/Lyst 的情况下溶酶体融合和裂变的速率。在这里，我们通过显微镜、流式细胞术和体外融合显示，Chs1/Lyst 蛋白的缺失不会增加溶酶体融合的速率。相反，我们的数据表明，这种蛋白质的缺失会降低溶酶体裂变的速率。我们进一步表明，Chs1/Lyst 蛋白的过表达会导致溶酶体裂变的速率加快。这些结果表明，Chs1/Lyst 通过影响裂变来调节溶酶体大小。
