Endoplasmic reticulum calcium storage and release in cells expressing misfolded growth hormone.

Aim: Deletion of amino acids 32-71 in human growth hormone (Delta 32-71-GH) causes severe autosomal dominant GH deficiency. These experiments test whether retention of Delta 32-71-GH in the endoplasmic reticulum (ER) lumen leads to aberrant Ca(2+) regulation.
Design: COS cells were transfected with Delta 32-71-GH, wild-type-GH or empty plasmid, and the ability of the cells to release Ca(2+) from the ER and transmit a Ca(2+) signal to the cytoplasm was investigated using cytoplasmic Ca(2+) dyes and ER-targeted cameleon Ca(2+) reporters.
Results: Resting free Ca(2+), the rate of Ca(2+) release from the ER and the size of the ionophore-releasable ER Ca(2+) pool were not altered by Delta 32-71-GH. Stimulation of endogenous Ca(2+)-mobilizing receptors for histamine and thrombin resulted in similar changes in cytoplasmic and ER Ca(2+) in cells expressing wild-type and Delta 32-71-GH.
Conclusion: Ca(2+) regulation is preserved despite retention of misfolded GH in the ER.