title: The Cellular Prion Protein Prevents Copper-Induced Inhibition of P2X(4) Receptors.
abstract: Although the physiological function of the cellular prion protein (PrP(C)) remains unknown, several evidences support the notion of its role in copper homeostasis. PrP(C) binds Cu(2+) through a domain composed by four to five repeats of eight amino acids. Previously, we have shown that the perfusion of this domain prevents and reverses the inhibition by Cu(2+) of the adenosine triphosphate (ATP)-evoked currents in the P2X(4) receptor subtype, highlighting a modulatory role for PrP(C) in synaptic transmission through regulation of Cu(2+) levels. Here, we study the effect of full-length PrP(C) in Cu(2+) inhibition of P2X(4) receptor when both are coexpressed. PrP(C) expression does not significantly change the ATP concentration-response curve in oocytes expressing P2X(4) receptors. However, the presence of PrP(C) reduces the inhibition by Cu(2+) of the ATP-elicited currents in these oocytes, confirming our previous observations with the Cu(2+) binding domain. Thus, our observations suggest a role for PrP(C) in modulating synaptic activity through binding of extracellular Cu(2+).
authors: Departamento de Fisiología, Centro de Envejecimiento y Regeneración (CARE), Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago 8331150, Chile.
authors: Ramón A
authors: RA
authors: Lorca
authors: Lorena
authors: L
authors: Varela-Nallar
authors: Nibaldo C
authors: NC
authors: Inestrosa
authors: J Pablo
authors: JP
authors: Huidobro-Toro