Kypri Elena, Schmauch Christian, Maniak Markus, De Lozanne Arturo
Section of Molecular Cell and Developmental Biology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.
Traffic. 2007 Jun;8(6):774-83. doi: 10.1111/j.1600-0854.2007.00567.x. Epub 2007 May 4.
The Chediak-Higashi syndrome (CHS) is a genetic disorder caused by the loss of the BEACH protein Lyst. Impaired lysosomal function in CHS patients results in many physiological problems, including immunodeficiency, albinism and neurological problems. Dictyostelium LvsB is the ortholog of mammalian Lyst and is also important for lysosomal function. A knock-in approach was used to tag LvsB with green fluorescent protein (GFP) and express it from its single chromosomal locus. GFP-LvsB was observed on late lysosomes and postlysosomes. Loss of LvsB resulted in enlarged postlysosomes, in the abnormal localization of proton pumps on postlysosomes and their abnormal acidification. The abnormal postlysosomes in LvsB-null cells were produced by the inappropriate fusion of early endosomal compartments with postlysosomal compartments. The intermixing of compartments resulted in a delayed transit of fluid-phase marker through the endolysosomal system. These results support the model that LvsB and Lyst proteins act as negative regulators of fusion by limiting the heterotypic fusion of early endosomes with postlysosomal compartments.
切迪阿克-东综合征（CHS）是一种由BEACH蛋白Lyst缺失引起的遗传性疾病。CHS患者的溶酶体功能受损会导致许多生理问题，包括免疫缺陷、白化病和神经问题。盘基网柄菌LvsB是哺乳动物Lyst的直系同源物，对溶酶体功能也很重要。采用基因敲入方法用绿色荧光蛋白（GFP）标记LvsB，并从其单染色体位点表达。在晚期溶酶体和后溶酶体上观察到GFP-LvsB。LvsB的缺失导致后溶酶体增大，质子泵在后溶酶体上的定位异常及其酸化异常。LvsB基因缺失细胞中的异常后溶酶体是由早期内体区室与后溶酶体区室的不适当融合产生的。区室的混合导致液相标记物通过内溶酶体系统的转运延迟。这些结果支持了LvsB和Lyst蛋白通过限制早期内体与后溶酶体区室之间的异型融合而作为融合负调节因子的模型。
