title: Down-regulation of Homer1b/c attenuates group I metabotropic glutamate receptors dependent Ca²⁺ signaling through regulating endoplasmic reticulum Ca²⁺ release in PC12 cells.
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 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.
authors.affiliation: 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.
authors.forename: Miao-Miao
authors.initials: MM
authors.lastname: Lv
authors.affiliation: Department of Anesthesiology, The Third Hospital of PLA, Baoji, Shaanxi 721004, China.
authors.forename: Yong-Chun
authors.initials: YC
authors.lastname: Cheng
authors.affiliation: Department of Anesthesiology, The 323 Hospital of PLA, Xi'an, Shaanxi 710054, China.
authors.forename: Zhi-Bin
authors.initials: ZB
authors.lastname: Xiao
authors.affiliation: Department of Anesthesiology, Tangdu Hospital of the Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Mei-Yan
authors.initials: MY
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Tangdu Hospital of the Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Peng-Cheng
authors.initials: PC
authors.lastname: Ren
authors.affiliation: Department of Anesthesiology, Tangdu Hospital of the Fourth Military Medical University, Xi'an, Shaanxi 710032, China. Electronic address: fmmusunxude@163.com.
authors.forename: Xu-De
authors.initials: XD
authors.lastname: Sun
mesh_terms: D000818:Animals; D001483:Base Sequence; D020013:Calcium Signaling; D002352:Carrier Proteins / Q000378:metabolism*; D017931:DNA Primers; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000072233:Homer Scaffolding Proteins; D016716:PC12 Cells; D034622:RNA Interference; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D000072233:Homer Scaffolding Proteins; D018094:Receptors, Metabotropic Glutamate
keywords: Calcium; Endoplasmic reticulum; Homer; RNAi; mGluRs