Regulation of protein sorting at the TGN by plasma membrane receptor activation.
We show that in the rat basophilic leukemia cell line RBL, the physiological stimulation of the IgE receptor or direct activation of PKC leads to the missorting of proteins to the plasma membrane, diverting them from their normal intracellular destination. This is demonstrated for two classes of proteins that are normally targeted to the secretory lysosomes via completely different mechanisms, i.e. proteoglycans and the aspartic protease cathepsin D. In the latter case, normal processing of the enzyme is also affected, leading to secretion of the immature form of cathepsin. The present study shows how completely different sorting mechanisms, such as those for delivering proteoglycans and cathepsin D to secretory lysosomes, might share common regulatory signals and are similarly affected when the levels of these signals are perturbed. Finally, protein kinase C appears to be a major player in the signal transduction pathways, leading to proteoglycan and cathepsin D missorting.
Baldassarre
M
M
Department of Cell Biology, Istituto di Ricerche Farmacologiche 'Mario Negri', Chieti 66030, Italy. buccione@cmns.mnegri.it
Dragonetti
A
A
Marra
P
P
Luini
A
A
Isidoro
C
C
Buccione
R
R
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D020126:Brefeldin A / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D002402:Cathepsin D / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006025:Glycosaminoglycans / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D015471:Leukemia, Basophilic, Acute; D008247:Lysosomes / Q000201:enzymology; D011493:Protein Kinase C / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017455:Receptors, IgE / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D006025:Glycosaminoglycans; D011500:Protein Synthesis Inhibitors; D017455:Receptors, IgE; D020126:Brefeldin A; D011493:Protein Kinase C; D010450:Endopeptidases; D002402:Cathepsin D; D013755:Tetradecanoylphorbol Acetate