Peptides derived from the human transferrin receptor stimulate endosomal acidification via a Gi-type protein11See Editorial by Warnock, p. 2524.

Peptides derived from the human transferrin receptor stimulate endosomal acidification via a Gi-type protein.BackgroundAcidification 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.MethodsSynthetic 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.ResultsPeptides activated the Gi, as evidenced by stimulation of the rate of GTPγS binding. A transferrin receptor peptide that lacked the KPKR sequence did not stimulate endosomal acidification and failed to promote GTPγS binding to Gi proteins.ConclusionsThese 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