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


BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Codina
J
J
University of Texas Houston Medical School, Houston, USA.
Gurich
R
R
Dubose
T D
TD
D000595:Amino Acid Sequence; D000818:Animals; D011992:Endosomes / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D010455:Peptides; D006180:Proton-Translocating ATPases / Q000378:metabolism; D011817:Rabbits; D011990:Receptors, Transferrin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014862:Wasp Venoms / Q000737:chemistry / Q000494:pharmacology
D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D010455:Peptides; D011990:Receptors, Transferrin; D014862:Wasp Venoms; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C037500:mastoparan; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D006180:Proton-Translocating ATPases