Novel zinc-responsive post-transcriptional mechanisms reciprocally regulate expression of the mouse Slc39a4 and Slc39a5 zinc transporters (Zip4 and Zip5).
Dietary zinc deficiency in mice is accompanied by enhanced expression of the zinc uptake transporter Slc39a4 (Zip4) and repressed expression of Slc39a5 (Zip5) in tissues which regulate zinc homeostasis (intestine, pancreas and visceral yolk sac). Herein, mechanisms controlling this differential expression were investigated. The induction of Zip4 mRNA during zinc deficiency, and its repression in response to zinc repletion were found to reflect changes in Zip4 mRNA stability and not changes in the relative rate of transcription of this gene. During zinc deficiency, ZIP4 protein levels are increased and this protein is localized on the apical membranes. Administration of an oral gavage of zinc caused ZIP4 internalization and degradation in enterocytes and visceral endoderm cells. Similarly, ZIP4 is induced by zinc deficiency in cultured mouse Hepa cells and is rapidly degraded in response to added zinc. Zip5 mRNA abundance does not change in response to zinc, but the translation of this mRNA was found to be zinc-responsive. During zinc deficiency, Zip5 mRNA remains associated with polysomes, while the protein is internalized and degraded in enterocytes, acinar cells and endoderm cells. After zinc-gavage, ZIP5 is rapidly resynthesized and targeted to the basolateral membranes of these cell types.
Weaver
Benjamin P
BP
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160-7421, USA. gandrews@kumc.edu
Dufner-Beattie
Jodi
J
Kambe
Taiho
T
Andrews
Glen K
GK
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D027682:Cation Transport Proteins / Q000096:biosynthesis* / Q000235:genetics*; D002460:Cell Line; D002499:Centrifugation, Density Gradient; D004032:Diet; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D007700:Kinetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009924:Organ Culture Techniques; D011132:Polyribosomes / Q000235:genetics; D011247:Pregnancy; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015017:Yolk Sac / Q000637:transplantation; D015032:Zinc / Q000494:pharmacology*
D027682:Cation Transport Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C477530:Slc39a4 protein, mouse; C494728:Slc39a5 protein, mouse; D015032:Zinc