THE EFFECT OF WORTMANNIN ON THE LOCALIZATION OF LYSOSOMAL TYPE-I INTEGRAL MEMBRANE-GLYCOPROTEINS SUGGESTS A ROLE FOR PHOSPHOINOSITIDE 3-KINASE ACTIVITY IN REGULATING MEMBRANE TRAFFIC LATE IN THE ENDOCYTIC PATHWAY

Addition of wortmannin to normal rat kidney cells caused a redistribut ion of the lysosomal type I integral membrane proteins lgp 110 and lgp 120 to a swollen vacuolar compartment. This compartment did not contai n the cation independent mannose 6-phosphate receptor and was depleted in acid hydrolases. It was distinct from another swollen vacuolar com partment containing the cation independent mannose 6-phosphate recepto r. The swollen lgp110-positive compartment was accessible to a monoclo nal antibody against lgp120 added extracellularly, showing that it had the characteristics of an endosomal compartment. Wortmannin had no gr oss morphological effect on the trans-Golgi network or lysosomes nor a ny effect on the delivery to the trans-Golgi network of endocytosed an tibodies against the type I membrane protein TGN38. We propose that th e observed effects of wortmannin were due to inhibition of membrane tr affic between cation independent mannose 6-phosphate receptor-positive late endosomes and the trans-Golgi network and to inhibition of membr ane traffic between a novel lgp120-positive, cation independent mannos e 6-phosphate receptor-negative late endosomal compartment and lysosom es. The effects of wortmannin suggest a function for a phosphatidylino sitol 3-kinase(s) in regulating membrane traffic in the late endocytic pathway.