Peters C, Braun M, Weber B, Wendland M, Schmidt B, Pohlmann R, Waheed A, von Figura K
Georg-August-Universität Göttingen, Abt. Biochemie II, FRG.
EMBO J. 1990 Nov;9(11):3497-506. doi: 10.1002/j.1460-2075.1990.tb07558.x.
Lysosomal acid phosphatase (LAP) is synthesized as a transmembrane protein with a short carboxy-terminal cytoplasmic tail of 19 amino acids, and processed to a soluble protein after transport to lysosomes. Deletion of the membrane spanning domain and the cytoplasmic tail converts LAP to a secretory protein, while deletion of the cytoplasmic tail as well as substitution of tyrosine 413 within the cytoplasmic tail against phenylalanine causes accumulation at the cell surface. A chimeric polypeptide, in which the cytoplasmic tail of LAP was fused to the ectoplasmic and transmembrane domain of hemagglutinin is rapidly internalized and tyrosine 413 of the LAP tail is essential for internalization of the fusion protein. A chimeric polypeptide, in which the membrane spanning domain and cytoplasmic tail of LAP are fused to the ectoplasmic domain of the Mr 46 kd mannose 6-phosphate receptor, is rapidly transported to lysosomes, whereas wild type receptor is not transported to lysosomes. We conclude that a tyrosine containing endocytosis signal in the cytoplasmic tail of LAP is necessary and sufficient for targeting to lysosomes.
溶酶体酸性磷酸酶（LAP）最初作为一种跨膜蛋白合成，其羧基末端有一段由19个氨基酸组成的短细胞质尾巴，在转运到溶酶体后加工成可溶性蛋白。删除跨膜结构域和细胞质尾巴会使LAP转变为分泌蛋白，而删除细胞质尾巴以及将细胞质尾巴内的酪氨酸413替换为苯丙氨酸会导致其在细胞表面积累。一种嵌合多肽，其中LAP的细胞质尾巴与血凝素的胞外和跨膜结构域融合，会迅速内化，并且LAP尾巴的酪氨酸413对于融合蛋白的内化至关重要。一种嵌合多肽，其中LAP的跨膜结构域和细胞质尾巴与46kd甘露糖6-磷酸受体的胞外结构域融合，会迅速转运到溶酶体，而野生型受体则不会转运到溶酶体。我们得出结论，LAP细胞质尾巴中含酪氨酸的内吞信号对于靶向溶酶体是必要且充分的。
