Prill V, Lehmann L, von Figura K, Peters C
Universität Göttingen, Germany.
EMBO J. 1993 May;12(5):2181-93. doi: 10.1002/j.1460-2075.1993.tb05866.x.
Lysosomal acid phosphatase (LAP) is synthesized as a type I membrane glycoprotein and targeted to lysosomes via the plasma membrane. Its cytoplasmic tail harbours a tyrosine-containing signal for rapid internalization. Expression in Madine-Darby canine kidney cells results in direct sorting to the basolateral cell surface, rapid endocytosis and delivery to lysosomes. In contrast, a deletion mutant lacking the cytoplasmic tail is delivered to the apical plasma membrane where it accumulates before it is slowly internalized. A chimeric protein, in which the cytoplasmic tail of LAP is fused to the extracytoplasmic and transmembrane domain of the apically sorted haemagglutinin, is sorted to the basolateral plasma membrane. A series of truncation and substitution mutants in the cytoplasmic tail was constructed and comparison of their polarized sorting and internalization revealed that the determinants for basolateral sorting and rapid internalization reside in the same segment of the cytoplasmic tail. The cytoplasmic factors decoding these signals, however, tolerate distinct mutations indicating that different receptors are involved in sorting at the trans-Golgi network and at the plasma membrane.
溶酶体酸性磷酸酶（LAP）作为I型膜糖蛋白被合成，并通过质膜靶向溶酶体。其细胞质尾部含有一个用于快速内化的含酪氨酸信号。在麦迪逊-达比犬肾细胞中的表达导致其直接分选至基底外侧细胞表面，随后快速内吞并转运至溶酶体。相比之下，缺失细胞质尾部的缺失突变体被转运至顶端质膜，在那里积累，之后才被缓慢内化。一种嵌合蛋白，其中LAP的细胞质尾部与顶端分选的血凝素的胞外和跨膜结构域融合，被分选至基底外侧质膜。构建了一系列细胞质尾部的截短和替代突变体，对它们的极性分选和内化进行比较后发现，基底外侧分选和快速内化的决定因素位于细胞质尾部的同一区段。然而，解码这些信号的细胞质因子能够耐受不同的突变，这表明在反式高尔基体网络和质膜的分选中涉及不同的受体。
