Different glycoforms of prostate-specific membrane antigen are intracellularly transported through their association with distinct detergent-resistant membranes

Deborah Castelletti , Marwan Alfalah , Martin Heine , Zeynep Isguder , Ruth Schmitte , Giulio Fracasso , Marco Colombatti , Hassan Y. Naim (1)

1 Professor and Chairman of Biochemistry; Department of Physiological Chemistry

Hormone-refractory prostate carcinomas as well as the neovasculature of different tumours express high levels of prostate-specific membrane antigen (PSMA). 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 detergent-resistant membranes (DRMs) at different stages of the protein maturation pathway in 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.

Mots clés: Life Sciences

Deborah Castelletti, Marwan Alfalah, Martin Heine, Zeynep Isguder, Ruth Schmitte, et al.. Different glycoforms of prostate-specific membrane antigen are intracellularly transported through their association with distinct detergent-resistant membranes. Biochemical Journal, 2007, 409 (1), pp.149-157. ⟨10.1042/BJ20070396⟩. ⟨hal-00478777⟩