title: Biosynthetic transport of a major lysosome-associated membrane glycoprotein 2, lamp-2: a significant fraction of newly synthesized lamp-2 is delivered to lysosomes by way of early endosomes.
abstract: Lysosomal membranes contain two highly glycosylated proteins, designated as lamp-1 and lamp-2, as major components. Lamp-1 and lamp-2 are similar to each other in the protein structure. Here, we investigated the biosynthetic transport of lamp-2 through the endocytic vacuoles in cultured rat hepatocytes in comparison with that of lamp-1, which has previously been studied [Akasaki et al. (1995) Exp. Cell Res. 220, 464-473]. Newly synthesized lamp-2 (NS-lamp-2) was transported to the trans-Golgi from rough endoplasmic reticulum with a half time (t1/2) of 32 min, more slowly than NS-lamp-1 (t1/2 = 13 min). After leaving the trans-Golgi, NS-lamp-2 is transferred to at least three compartments; the cell surface (t1/2 = 47 min), cell peripheral early endosomes (t1/2 = 38 min) and perinuclear late endosomes (t1/2 = 48 min). NS-lamp-2 transported to any compartment is delivered finally to lysosomes (t1/2 = 90 min). A significant fraction of NS-lamp-2 (45% of the total) was transported from the trans-Golgi to early endosomes, and then delivered to dense lysosomes via perinuclear late endosomes, whereas a major portion of NS-lamp-1 follows an intracellular route to late endosomes without passing through the cell periphery. NS-lamp-2 leaves the cell peripheral region more rapidly than NS-lamp-1. The kinetic and quantitative data for biosynthetic transport of NS-lamp-2 to early endosomes and the cell surface indicate that NS-lamp-2 may be transported first to early endosomes, from which a small portion of it (approximately 3.5% of the total) moves to the plasma membrane via a recycling system. In contrast, a small fraction of NS-lamp-1 is transported to the plasma membrane directly from the trans-Golgi, since NS-lamp-1 is delivered to the plasma membrane and early endosomes with almost the same half times.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Hiroshima.
authors.forename: K
authors.initials: K
authors.lastname: Akasaki
authors.forename: A
authors.initials: A
authors.lastname: Michihara
authors.forename: Y
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: K
authors.initials: K
authors.lastname: Mibuka
authors.forename: H
authors.initials: H
authors.lastname: Tsuji
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D001693:Biological Transport, Active; D002478:Cells, Cultured; D002645:Chickens; D004591:Electrophoresis, Polyacrylamide Gel; D011992:Endosomes / Q000378:metabolism*; D006801:Humans; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D016415:Sequence Alignment
chemical_list: D015703:Antigens, CD; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins