Detergent-resistant membranes are essential along the signalling pathways of prostate-specific membrane antigen

Prostate-specific membrane antigen (PSMA) is a surface protein overexpressed in prostate cancer and neovasculature of further tumours. It is therefore one of the most promising biomarkers in diagnosis and treatment of prostate cancer.

PSMA is associated with detergent-resistant membranes (DRMs). The mature form of PSMA is mainly insoluble in Lubrol WX, but does not associate with Triton X-100 DRMs.

Recently we could demonstrate that cross-linking of cell surface PSMA with specific antibodies activates different signalling cascades like the MAPK-pathway. Here we show that internalization of PSMA is increased after antibody binding and this leads to redistribution of PSMA to Triton X-100 DRMs in a time-dependent manner and to alterations in the expression levels of several proteins in these DRMs. One of these proteins is laminin receptor-1 which directly interacts with PSMA in co-immunoprecipitation experiments.

Our results propose an essential role for different DRM types in the signalling pathways involving PSMA.