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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Underhill, D. M. Articles by Schwartz, A. L. Search for Related Content PubMed PubMed Citation Articles by Underhill, D. M. Articles by Schwartz, A. L. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Endocytosis and lysosomal delivery of tissue plasminogen activator- inhibitor 1 complexes in Hep G2 cells DM Underhill, DA Owensby, PA Morton and AL Schwartz Edward Mallinckrodt Departments of Cell Biology, St Louis Children's Hospital, Washington University School of Medicine, MO. Receptor-mediated endocytosis of tissue-type plasminogen activator (t- PA)-plasminogen activator inhibitor type 1 (PAI-1) complexes results in their clearance by Hep G2 cells. After complexes are internalized, the t-PA component is degraded. However, neither the locus of intracellular catabolism nor the fate of PAI-1 has been elucidated. To characterize these aspects of t-PA-PAI-1 catabolism, the subcellular distribution of a prebound cohort of ligand molecules was delineated after internalization at 37 degrees C. 125I-t-PA.PAI-1 and t-PA.125I-PAI-1 were compared in separate experiments. After ligand uptake, intracellular vesicles were separated on density gradients. Internalized 125I-t-PA.PAI-1 concentrated initially in endosomes. After 20 minutes of uptake, the complex began to appear in lysosomes. Subsequently, low molecular weight labeled ligand fragments were detected in culture media. A panel of lysosomotropic agents, including primaquine, chloroquine, ammonium chloride, and a combination of leupeptin and pepstatin A, inhibited degradation. When t-PA.125I-PAI-1 rather than 125I-t-PA.PAI-1 was internalized, strikingly different results were observed. Although the kinetics of internalization and the intracellular itinerary were indistinguishable for the differently labeled complexes, the 125I-PAI-1 component of t-PA.125I-PAI-1 resisted rapid degradation. After a rapid loss of t-PA, the 125I-PAI-1 moiety persisted in lysosomes for up to 180 minutes. Thus, internalized t- PA.PAI-1 is targeted to lysosomes in which PAI-1 is relatively more stable than t-PA. Volume 80, Issue 11, pp. 2746-2754, 12/01/1992 Copyright © 1992 by The American Society of Hematology CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Ho, J. R. Toomey, G. J. Broze Jr., and A. L. Schwartz Receptor-mediated Endocytosis of Coagulation Factor Xa Requires Cell Surface-bound Tissue Factor Pathway Inhibitor J. Biol. Chem., April 19, 1996; 271(16): 9497 - 9502. [Abstract] [Full Text] [PDF]

	Copyright © 1992 by American Society of Hematology         Online ISSN: 1528-0020