Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8297483 | Biochemical and Biophysical Research Communications | 2014 | 7 Pages |
Abstract
The molecular basis for group I metabotropic glutamate receptors (mGluR1 and 5) coupling to membrane ion channels and intracellular calcium pools is not fully understood. Homer is a family of post synaptic density proteins functionally and physically attached to target proteins at proline-rich sequences. In the present study, we demonstrate that Homer1b/c is constitutively expressed in PC12 cells, whereas Homer1a, the immediate early gene product, can be up-regulated by brain derived neurotrophic factor (BDNF) and glutamate. Knockdown of Homer1b/c using specific target small interfering RNA (siRNA) did not interfere the expression of mGluR1, mGluR5 and their downstream effectors, including inositol-1,4,5-trisphosphate receptors (IP3R), phospholipase C (PLC) and Gq proteins. By analyzing Ca2+ imaging in PC12 cells, we demonstrated that Homer1b/c is an essential regulator of the Ca2+ release from the endoplasmic reticulum (ER) induced by the activation of group I mGluRs, IP3R and ryanodine receptors (RyR). Furthermore, the group I mGluRs activation-dependent refilling of the Ca2+ stores in both resting and depolarizing conditions were strongly attenuated in the absence of Homer1b/c. Together, our results demonstrate that in PC12 cells Homer1b/c is a regulator of group I mGluRs related Ca2+ homeostasis that is essential for the maintenance of normal Ca2+ levels in the ER.
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Authors
Miao-Miao Lv, Yong-Chun Cheng, Zhi-Bin Xiao, Mei-Yan Sun, Peng-Cheng Ren, Xu-De Sun,