Reaves B J, Bright N A, Mullock B M, Luzio J P
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, UK.
J Cell Sci. 1996 Apr;109 ( Pt 4):749-62. doi: 10.1242/jcs.109.4.749.
Addition of wortmannin to normal rat kidney cells caused a redistribution of the lysosomal type I integral membrane proteins Igp110 and Igp120 to a swollen vacuolar compartment. This compartment did not contain the cation independent mannose 6-phosphate receptor and was depleted in acid hydrolases. It was distinct from another swollen vacuolar compartment containing the cation independent mannose 6-phosphate receptor. The swollen Igp110-positive compartment was accessible to a monoclonal antibody against Igp120 added extracellularly, showing that it had the characteristics of an endosomal compartment. Wortmannin had no gross morphological effect on the trans-Golgi network or lysosomes nor any effect on the delivery to the trans-Golgi network of endocytosed antibodies against the type I membrane protein TGN38. We propose that the observed effects of wortmannin were due to inhibition of membrane traffic between cation independent mannose 6-phosphate receptor-positive late endosomes and the trans-Golgi network and to inhibition of membrane traffic between a novel Igp120-positive, cation independent mannose 6-phosphate receptor-negative late endosomal compartment and lysosomes. The effects of wortmannin suggest a function for a phosphatidylinositol 3-kinase(s) in regulating membrane traffic in the late endocytic pathway.
向正常大鼠肾细胞中添加渥曼青霉素会导致溶酶体I型整合膜蛋白Igp110和Igp120重新分布到一个肿胀的液泡区室。这个区室不包含阳离子非依赖性甘露糖6-磷酸受体，且酸性水解酶含量减少。它与另一个含有阳离子非依赖性甘露糖6-磷酸受体的肿胀液泡区室不同。添加到细胞外的抗Igp120单克隆抗体可进入肿胀的Igp110阳性区室，表明它具有内体区室的特征。渥曼青霉素对反式高尔基体网络或溶酶体没有明显的形态学影响，对针对I型膜蛋白TGN38的内吞抗体向反式高尔基体网络的转运也没有影响。我们认为，渥曼青霉素观察到的效应是由于抑制了阳离子非依赖性甘露糖6-磷酸受体阳性晚期内体与反式高尔基体网络之间的膜运输，以及抑制了一个新的Igp120阳性、阳离子非依赖性甘露糖6-磷酸受体阴性晚期内体区室与溶酶体之间的膜运输。渥曼青霉素的效应表明磷脂酰肌醇3-激酶在调节晚期内吞途径中的膜运输方面具有功能。
