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bioRxiv · 10.1101/2020.09.09.290114

Stanniocalcin 1a is a Ca2+-regulated switch controlling epithelial cell quiescence-proliferation balance and Ca2+ uptake

Li, S.·Liu, C.·Goldstein, A.·Xin, Y.·Ke, C.·Duan, C.
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Abstract

The mechanisms governing cell quiescence-proliferation balance are poorly defined. Using a zebrafish model, here we report that Stc1a, a glycoprotein known as a hypocalcemic hormone, not only inhibits epithelial calcium uptake but also functions as a Ca2+-regulated switch controlling epithelial cell quiescence-proliferation balance. Among the 4 stc genes, only the stc1a expression is [Ca2+]-dependent. Genetic deletion of stc1a, but not stc2b, resulted in elevated body Ca2+ contents, ectopic Ca2+ deposit, body swelling, and premature death. Reducing epithelial calcium channel Trpv6-mediated Ca2+ uptake alleviated these phenotypes. Loss of Stc1a also promoted quiescent epithelial cells to re-enter the cell cycle. This action was accompanied by local IGF signaling activation and increased expression in papp-aa, a zinc metalloproteinase degrading Igfbp5a. Genetic deletion of papp-aa or igfbp5a abolished the elevated epithelial cell reactivation in stc1a-/- mutants. Likewise, inhibition of IGF1 receptor, PI3 kinase, Akt, and Tor signaling abolished epithelial cell reactivation. These results reveal that Stc1a plays dual roles in regulating epithelial calcium uptake and cell quiescence-proliferation balance and implicate Trpv6 and Papp-aa-Igfbp5a-IGF signaling in these functions.

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Li, S., Liu, C., Goldstein, A., Xin, Y., Ke, C., Duan, C.. 2020-09-10. Stanniocalcin 1a is a Ca2+-regulated switch controlling epithelial cell quiescence-proliferation balance and Ca2+ uptake. https://doi.org/10.1101/2020.09.09.290114

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