Different glycoforms of prostate-specific membrane antigen are intracellularly transported through their association with distinct detergent-resistant membranes.
Hormone-refractory prostate carcinomas as well as the neovasculature of different tumours express high levels of PSMA (prostate-specific membrane antigen). PSMA is a type II-transmembrane glycoprotein and a potential tumour marker for both diagnosis and passive immunotherapy. Here, we report on the association of PSMA with DRMs (detergent-resistant membranes) at different stages of the protein maturation pathway in human prostate carcinoma LNCaP cells. At least three PSMA glycoforms were biochemically identified based on their extractability behaviour in different non-ionic detergents. In particular, one precursor glycoform of PSMA is associated with Tween 20-insoluble DRMs, whereas the complex glycosylated protein segregates into membrane structures that are insoluble in Lubrol WX and display a different lipid composition. Association of PSMA with these membranes occurs in the Golgi compartment together with the acquisition of a native conformation. PSMA homodimers reach the plasma membrane of LNCaP cells in Lubrol WX-insoluble lipid/protein complexes. At the steady state, the majority of PSMA remains within these membrane microdomains at the cell surface. We conclude that the intracellular transport of PSMA occurs through populations of DRMs distinct for each biosynthetic form and cellular compartment.
Castelletti
Deborah
D
Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, Germany.
Alfalah
Marwan
M
Heine
Martin
M
Hein
Zeynep
Z
Schmitte
Ruth
R
Fracasso
Giulio
G
Colombatti
Marco
M
Naim
Hassan Y
HY
D000941:Antigens / Q000737:chemistry; D000954:Antigens, Surface / Q000737:chemistry* / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D003902:Detergents / Q000494:pharmacology*; D043425:Glutamate Carboxypeptidase II / Q000737:chemistry* / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry*; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008297:Male; D021962:Membrane Microdomains; D008566:Membranes / Q000737:chemistry*; D017830:Octoxynol / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology; D011136:Polysorbates / Q000494:pharmacology; D020033:Protein Isoforms; D020836:Protein Structure, Quaternary
D000941:Antigens; D000954:Antigens, Surface; D003902:Detergents; D006023:Glycoproteins; D008055:Lipids; D011136:Polysorbates; D020033:Protein Isoforms; C017474:Lubrol WX; D011092:Polyethylene Glycols; D017830:Octoxynol; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II