BIOSYNTHETIC TRANSPORT OF A MAJOR LYSOSOMAL MEMBRANE GLYCOPROTEIN, LAMP-1 - CONVERGENCE OF BIOSYNTHETIC AND ENDOCYTIC PATHWAYS OCCURS AT 3 DISTINCTIVE POINTS

We studied the kinetics of the biosynthetic transport of lysosome-associated membrane glycoprotein-1 (lamp-1) to the endocytic compartments in cultured rat hepatocytes. Newly synthesized lamp-1 (NS-lamp-1) was transported to the trans-Golgi from rough endoplasmic: reticulum with a half time (t(1/2)) of 13 min. From the trans-Golgi, at least 25% of NS-lamp-1 was delivered to the cell periphery: to the cell surface and early endosomes with t(1/2) s of 32 and 33 min, respectively. A comparison of the kinetics of the biosynthetic transport of lamp-1 to both compartments demonstrated that NS-lamp-1 takes two peripheral routes from the Golgi apparatus; it is delivered to early endosomes directly and after reaching the cell surface. A major portion of NS-lamp-l follows a direct intracellular pathway to late endosomes (t(1/2) = 45 min) and subsequently to lysosomes (t(1/2) = 85 min). The kinetic data of the biosynthetic transport to these endocytic vacuoles suggested that a significant fraction of NS-lamp-1 returns to the late endosomes immediately after its arrival at lysosomes and that there is a unique retrograde delivery of NS-lamp-1 from late to early endosomes prior to its transport to lysosomes. Thus, in cultured rat hepatocytes, the lamp-1 biosynthetic and the endocytic pathways converge at the three distinctive points. Late endosomes are centrally situated in the complex biosynthetic route of lamp-1. (C) 1995 Academic Press, Inc.