PMID- 25026550 OWN - NLM STAT- MEDLINE DCOM- 20141104 LR - 20161125 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 450 IP - 4 DP - 2014 Aug 8 TI - Down-regulation of Homer1b/c attenuates group I metabotropic glutamate receptors dependent Ca(2)(+) signaling through regulating endoplasmic reticulum Ca(2)(+) release in PC12 cells. PG - 1568-74 LID - S0006-291X(14)01271-6 [pii] LID - 10.1016/j.bbrc.2014.07.044 [doi] AB - 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 Ca(2+) imaging in PC12 cells, we demonstrated that Homer1b/c is an essential regulator of the Ca(2+) 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 Ca(2+) 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 Ca(2+) homeostasis that is essential for the maintenance of normal Ca(2+) levels in the ER. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Lv, Miao-Miao AU - Lv MM AD - Department of Anesthesiology, Tangdu Hospital of the Fourth Military Medical University, Xi'an, Shaanxi 710032, China; Department of Anesthesiology, The 323 Hospital of PLA, Xi'an, Shaanxi 710054, China. FAU - Cheng, Yong-Chun AU - Cheng YC AD - Department of Anesthesiology, The Third Hospital of PLA, Baoji, Shaanxi 721004, China. FAU - Xiao, Zhi-Bin AU - Xiao ZB AD - Department of Anesthesiology, The 323 Hospital of PLA, Xi'an, Shaanxi 710054, China. FAU - Sun, Mei-Yan AU - Sun MY AD - Department of Anesthesiology, Tangdu Hospital of the Fourth Military Medical University, Xi'an, Shaanxi 710032, China. FAU - Ren, Peng-Cheng AU - Ren PC AD - Department of Anesthesiology, Tangdu Hospital of the Fourth Military Medical University, Xi'an, Shaanxi 710032, China. FAU - Sun, Xu-De AU - Sun XD AD - Department of Anesthesiology, Tangdu Hospital of the Fourth Military Medical University, Xi'an, Shaanxi 710032, China. Electronic address: fmmusunxude@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140712 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Carrier Proteins) RN - 0 (DNA Primers) RN - 0 (Homer Scaffolding Proteins) RN - 0 (Receptors, Metabotropic Glutamate) SB - IM MH - Animals MH - Base Sequence MH - *Calcium Signaling MH - Carrier Proteins/*metabolism MH - DNA Primers MH - *Down-Regulation MH - Endoplasmic Reticulum/*metabolism MH - Homer Scaffolding Proteins MH - PC12 Cells MH - RNA Interference MH - Rats MH - Real-Time Polymerase Chain Reaction MH - Receptors, Metabotropic Glutamate/*metabolism OTO - NOTNLM OT - Calcium OT - Endoplasmic reticulum OT - Homer OT - RNAi OT - mGluRs EDAT- 2014/07/16 06:00 MHDA- 2014/11/05 06:00 CRDT- 2014/07/16 06:00 PHST- 2014/06/29 00:00 [received] PHST- 2014/07/07 00:00 [accepted] PHST- 2014/07/16 06:00 [entrez] PHST- 2014/07/16 06:00 [pubmed] PHST- 2014/11/05 06:00 [medline] AID - S0006-291X(14)01271-6 [pii] AID - 10.1016/j.bbrc.2014.07.044 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2014 Aug 8;450(4):1568-74. doi: 10.1016/j.bbrc.2014.07.044. Epub 2014 Jul 12.