Peptides derived from the human transferrin receptor stimulate endosomal acidification via a Gi-type protein.

Abstract

Peptides derived from the human transferrin receptor stimulate endosomal acidification via a Gi-type protein. Acidification of the endosomal compartment is a prerequisite for intracellular processing of endocytosed complexes. Endosomal acidification is accomplished by an H+-ATPase, in parallel with a Cl- conductance. Previous studies from our laboratory have demonstrated that endosomal acidification is modulated by a pertussis toxin-sensitive mechanism, suggesting that endosomal acidification could be regulated through a self-contained signal transduction pathway. This study was designed to test this hypothesis using the transferrin receptor as a model. Synthetic peptides corresponding to a region of the cytosolic domain of the transferrin receptor and containing a KPKR sequence were used to stimulate endosomal acidification in a G-protein-dependent manner. Peptides activated the Gi, as evidenced by stimulation of the rate of GTPgammaS binding. A transferrin receptor peptide that lacked the KPKR sequence did not stimulate endosomal acidification and failed to promote GTPgammaS binding to Gi proteins. These results demonstrate that regulation of endosomal acidification can be achieved, in part, through a Gi-mediated signal transduction pathway. These findings suggest that regulation of endosomal acidification through such a pathway may facilitate intracellular processing of the transferrin receptor.