Association of cellular prion protein with gangliosides in plasma membrane microdomains of neural and lymphocytic cells.
In this report we demonstrated that cellular prion protein is strictly associated with gangliosides in microdomains of neural and lymphocytic cells. We preliminarily investigated the protein distribution on the plasma membrane of human neuroblastoma cells, revealing the presence of large clusters. In order to evaluate its possible role in tyrosine signaling pathway triggered by GEM, we analyzed PrPc presence in microdomains and its association with gangliosides, using cholera toxin as a marker of GEM in neuroblastoma cells and anti-GM3 MoAb for identification of GEM in lymphoblastoid cells. In neuroblastoma cells scanning confocal microscopical analysis revealed a consistent colocalization between PrPc and GM1 despite an uneven distribution of both on the cell surface, indicating the existence of PrPc-enriched microdomains. In lymphoblastoid T cells PrPc molecules were mainly, but not exclusively, colocalized with GM3. In addition, PrPc was present in the Triton-insoluble fractions, corresponding to GEM of cell plasma membrane. Additional evidence for a specific PrPc-GM3 interaction in these cells was derived from the results of TLC analysis, showing that prion protein was associated with GM3 in PrPc immunoprecipitates. The physical association of PrPc with ganglioside GM3 within microdomains of lymphocytic cells strongly suggests a role for PrPc-GM3 complex as a structural component of the multimolecular signaling complex involved in T cell activation and other dynamic lymphocytic plasma membrane functions.
Mattei
Vincenzo
V
Dip. Medicina Sperimentale e Patologia, Università La Sapienza, Roma, Italy.
Garofalo
Tina
T
Misasi
Roberta
R
Gizzi
Chiara
C
Mascellino
Maria Teresa
MT
Dolo
Vincenza
V
Pontieri
Giuseppe M
GM
Sorice
Maurizio
M
Pavan
Antonio
A
D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D018621:PrPC Proteins / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D014407:Tumor Cells, Cultured
D005732:Gangliosides; D018621:PrPC Proteins