First published online December 21, 2005
Journal of Cell Science 119, 104e (2006)
© The Company of Biologists Limited
PERKing up Ca2+ signalling
The endoplasmic reticulum (ER) is involved in the biosynthesis of secretory proteins and the regulation of the Ca2+ signalling events that control their secretion. On p. 153, Shmuel Muallem and co-workers reveal a connection between these two functions by examining Ca2+ signalling in secretory cells and in muscle cells (which have a specialized ER called the sarcoplasmic reticulum, SR) from PERK-knockout mice. PERK (pancreatic ER kinase) attenuates protein synthesis in cells in which protein folding is disrupted, thus preventing the development of ER/SR stress. The authors report that, in PERK-null cells, ER/SR stress reduces the rate and efficiency of Ca2+ release from the ER/SR and disrupts the integrity of Ca2+ signalling complexes. These changes in Ca2+ signalling help to explain the decline in secretory cell function in PERK-knockout mice and implicate chronic ER/SR stress in the development of some human conditions. For example, suggest the authors, disruption of Ca2+ release by chronic ER/SR stress in pancreatic?-cells and myocytes could contribute to the defects in regulated insulin secretion and cardiac function seen in diabetes.

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Related articles in JCS:
- ER stress disrupts Ca2+-signaling complexes and Ca2+ regulation in secretory and muscle cells from PERK-knockout mice
- Guojin Huang, Jian Yao, Weizhong Zeng, Yusuke Mizuno, Kristine E. Kamm, James T. Stull, Heather P. Harding, David Ron, and Shmuel Muallem
JCS 2006 119: 153-161.
[Abstract]
[Full Text]