Document 0878
 DOCN  M9540878
 TI    Transport of a lysosomally targeted Rous sarcoma virus envelope
       glycoprotein involves transient expression on the cell surface.
 DT    9504
 AU    Johnston PB; Dong JY; Hunter E; Department of Microbiology, University
       of Alabama at Birmingham; 35294.
 SO    Virology. 1995 Jan 10;206(1):353-61. Unique Identifier : AIDSLINE
       MED/95133168
 AB    The details of intracellular transport pathways for glycosylated
       proteins remain incompletely described. We previously described a mutant
       Rous sarcoma virus envelope glycoprotein (gp), mu 26, with an altered
       membrane-spanning domain that was targeted to lysosomes after traversing
       the trans-Golgi. This mutant protein was not detectable on the cell
       surface by immunofluorescence, but its pathway for degradation remained
       unclear. To investigate this we have employed a second env mutation,
       S19, that results in a protein which is defective for normal
       cleavage/activation by intracellular enzymes, but remains susceptible to
       cleavage by extracellular proteases. Cleavage/activation of the double
       mutant by trypsin, which could only occur if it was exposed on the cell
       surface, was observed, indicating that the plasma membrane is an
       intermediate destination in the transport of this mutant protein. To
       substantiate these results, cells expressing the mu 26 glycoprotein were
       incubated with an antibody specific for the native protein in the
       presence of chloroquine. The specific accumulation of this antibody/gp
       complex in vesicles, as detected by internal immunofluorescence,
       confirmed the trypsin cleavage results. We conclude that this rapidly
       degraded mutant protein is transported from the trans-Golgi to the cell
       surface, where it is only transiently exposed, and then rapidly
       endocytosed and lysosomally degraded. The relevance of these results to
       the targeting of lysosomal proteins is discussed.
 DE    Amino Acid Sequence  Animal  Antibodies/IMMUNOLOGY  Biological Transport
       Cell Line  Cell Membrane/METABOLISM  Cercopithecus aethiops
       Chloroquine/PHARMACOLOGY  Endocytosis  Genes, env
       Glycoproteins/*METABOLISM  Lysosomes/DRUG EFFECTS/*METABOLISM  Molecular
       Sequence Data  Neutralization Tests  Sarcoma Viruses,
       Avian/GENETICS/IMMUNOLOGY/*METABOLISM  Support, Non-U.S. Gov't  Support,
       U.S. Gov't, P.H.S.  Viral Envelope Proteins/*METABOLISM  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).