Copper exposure induces trafficking of the menkes protein in intestinal epithelium of ATP7A transgenic mice.
The final steps in the absorption and excretion of copper at the molecular level are accomplished by 2 closely related proteins that catalyze the ATP-dependent transport of copper across the plasma membrane. These proteins, ATP7A and ATP7B, are encoded by the genes affected in human genetic copper-transport disorders, namely, Menkes and Wilson diseases. We studied the effect of copper perfusion of an isolated segment of the jejunum of ATP7A transgenic mice on the intracellular distribution of ATP7A by immunofluorescence of frozen sections. Our results indicate that ATP7A is retained in the trans-Golgi network under copper-limiting conditions, but relocalized to a vesicular compartment adjacent to the basolateral membrane in intestines perfused with copper. The findings support the hypothesis that the basolateral transport of copper from the enterocyte into the portal blood may involve ATP7A pumping copper into a vesicular compartment followed by exocytosis to release the copper, rather than direct pumping of copper across the basolateral membrane.
Monty
Jean-François
JF
Center for Cellular and Molecular Biology, School of Biological and Chemical Sciences, Deakin University, Burwood, Victoria, Australia.
Llanos
Roxana M
RM
Mercer
Julian F B
JF
Kramer
David R
DR
D000251:Adenosine Triphosphatases / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D003300:Copper / Q000494:pharmacology*; D000073840:Copper-Transporting ATPases; D017931:DNA Primers; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D016376:Oligonucleotides, Antisense; D010957:Plasmids; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D012834:Silver / Q000494:pharmacology
D027682:Cation Transport Proteins; D017931:DNA Primers; D016376:Oligonucleotides, Antisense; D011993:Recombinant Fusion Proteins; D012834:Silver; D003300:Copper; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases