Roles of LAMP-1 and LAMP-2 in lysosome biogenesis and autophagy
Roles of LAMP-1 and LAMP-2 in lysosome biogenesis and autophagy
复制标题
DOI：
10.1016/j.mam.2006.08.005
复制
发表时间：
2006-10-01
影响因子：
10.6
通讯作者：
Eskelinen, Eeva-Liisa
中科院分区：
文献类型：
--
作者：
Eskelinen, Eeva-Liisa
溶酶体膜蛋白LAMP-1和LAMP-2约占溶酶体膜蛋白的50%。令人惊讶的是，LAMP-1或LAMP-2基因缺失的小鼠仍然存活并具有生育能力。然而，同时缺乏LAMP-1和LAMP-2的小鼠具有胚胎致死表型。这些结果表明，这两种主要的溶酶体膜蛋白在体内具有共同的功能。然而，LAMP-2似乎具有更特殊的功能，因为LAMP-2的单一缺陷比LAMP-1的单一缺陷有更严重的后果。LAMP-2基因的突变会导致人类的一种溶酶体糖原储存疾病--达农病。LAMP-2基因缺陷小鼠复制了达农患者的症状，包括心脏和骨骼肌中积累的自噬空泡。在胚胎成纤维细胞中，两个LAMP的相互破坏与自噬空泡和未酯化胆固醇的积累增加有关，而蛋白质降解率不受影响。这些结果清楚地表明，LAMP蛋白在维持溶酶体隔室的结构完整性方面发挥的功能远远超出了最初提出的功能。(C)2006爱思唯尔有限公司。保留所有权利。
The lysosomal membrane proteins LAMP-1 and LAMP-2 are estimated to contribute to about 50% of all proteins of the lysosome membrane. Surprisingly, mice deficient in either LAMP-1 or LAMP-2 are viable and fertile. However, mice deficient in both LAMP-1 and LAMP-2 have an embryonic lethal phenotype. These results show that these two major lysosomal membrane proteins share common functions in vivo. However, LAMP-2 seems to have more specific functions since LAMP-2 single deficiency has more severe consequences than LAMP-1 single deficiency. Mutations in LAMP-2 gene cause a lysosomal glycogen storage disease, Danon disease, in humans. LAMP-2 deficient mice replicate the symptoms found in Danon patients including accumulation of autophagic vacuoles in heart and skeletal muscle. In embryonic fibroblasts, mutual disruption of both LAMPs is associated with an increased accumulation of autophagic vacuoles and unesterified cholesterol, while protein degradation rates are not affected. These results clearly show that the LAMP proteins fulfil functions far beyond the initially suggested roles in maintaining the structural integrity of the lysosomal compartment. (c) 2006 Elsevier Ltd. All rights reserved.