Signaling induced by hop/STI-1 depends on endocytosis.
The co-chaperone hop/STI-1 is a ligand of the cell surface prion protein (PrP(C)), and their interaction leads to signaling and biological effects. Among these, hop/STI-1 induces proliferation of A172 glioblastoma cells, dependent on both PrP(C) and activation of the Erk pathway. We tested whether clathrin-mediated endocytosis affects signaling induced by hop/STI-1. Both hyperosmolarity induced by sucrose and monodansyl-cadaverine blocked Erk activity induced by hop/STI-1, without affecting the high basal Akt activity typical of A172. The endocytosis inhibitors also affected the sub-cellular distribution of phosphorylated Erk, consistent with blockade of the latter's activity. The data indicate that signaling induced by hop/STI-1 depends on endocytosis. These findings are consistent with a role of sub-cellular trafficking in signal transduction following engagement by PrP(C) by ligands such as hop/STI-1, and may help help unravel both the functions of the prion protein, as well as possible loss-of-function components of prion diseases.
Americo
Tatiana A
TA
Instituto de Biofísica da UFRJ, Centro de Ciências da Saúde, bloco G, Cidade Universitária, Rio de Janeiro, Brazil.
Chiarini
Luciana B
LB
Linden
Rafael
R
D045744:Cell Line, Tumor; D004705:Endocytosis; D005909:Glioblastoma / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D018621:PrPC Proteins / Q000378:metabolism*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
C476884:HOPX protein, human; D018398:Homeodomain Proteins; D018621:PrPC Proteins; D025521:Tumor Suppressor Proteins