AI Article Synopsis
- Zinc transporters, specifically ZnT5 and ZnT6, are crucial for various biochemical processes, particularly in the secretory pathway of cells.
- In studies with ZnT5(-)ZnT7(-/-) cells, human tissue-nonspecific alkaline phosphatase (ALP) activity was significantly reduced, leading to proteasome-mediated degradation instead of reaching the plasma membrane.
- The expression of ZnT5 mRNA increases in response to endoplasmic reticulum stress, regulated by the transcription factor XBP1, indicating a tightly controlled mechanism for zinc transport that is vital for maintaining the function of the secretory pathway in vertebrate cells.
Article Abstract
Zinc transporters play important roles in a wide range of biochemical processes. Here we report an important function of ZnT5/ZnT6 hetero-oligomeric complexes in the secretory pathway. The activity of human tissue-nonspecific alkaline phosphatase (ALP) expressed in ZnT5(-)ZnT7(-/-) cells was significantly reduced compared with that expressed in wild-type cells as in the case of endogenous chicken tissue-nonspecific ALP activity. The inactive human tissue-nonspecific ALP in ZnT5(-)ZnT7(-/-) cells was degraded by proteasome-mediated degradation without being trafficked to the plasma membrane. ZnT5(-)ZnT7(-/-) cells showed exacerbation of the unfolded protein response as did the wild-type cells cultured under a zinc-deficient condition, revealing that both complexes play a role in homeostatic maintenance of secretory pathway function. Furthermore, we showed that expression of ZnT5 mRNA was up-regulated by the endoplasmic reticulum stress in various cell lines. The up-regulation of the hZnT5 transcript was mediated by transcription factor XBP1 through the TGACGTGG sequence in the hZnT5 promoter, and this sequence was highly conserved in the ZnT5 genes of mouse and chicken. These results suggest that zinc transport into the secretory pathway is strictly regulated for the homeostatic maintenance of secretory pathway function in vertebrate cells.
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| http://dx.doi.org/10.1074/jbc.M602470200 | DOI Listing |
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