title: Lipid rafts serve as signaling platforms for mGlu1 receptor-mediated calcium signaling in association with caveolin.
abstract: BACKGROUND
  Group I metabotropic glutamate receptors (mGlu1/5 receptors) have important roles in synaptic activity in the central nervous system. They modulate neuronal excitability by mobilizing intracellular Ca2+ following receptor activation. Also, accumulating evidence has indicated the association of Ca2+ signaling with lipid rafts. Caveolin, an adaptor protein found in a specialized subset of lipid rafts, has been reported to promote the localization of membrane proteins to lipid rafts.
  
  
  RESULTS
  In the present study, we investigated the role of lipid rafts on the mGlu1α receptor-mediated Ca2+ signaling in association with caveolin in hippocampal primary neurons and HEK293 cells. We show that the disruption of lipid rafts using methyl-β-cyclodextrin markedly decreased mGlu1α receptor-mediated Ca2+ transients and lipid rafts localization of the receptor. Furthermore, transfection of mGlu1α receptor with mutated caveolin-binding domain reduced localization of the receptor to lipid rafts. Also, application of a peptide blocker of mGlu1α receptor and caveolin binding reduced the Ca2+ signaling and the lipid rafts localization.
  
  
  CONCLUSIONS
  Taken together, these results suggest that the binding of mGlu1α receptor to caveolin is crucial for its lipid rafts localization and mGlu1α receptor-mediated Ca2+ transients.
authors: Seung-Eon
authors: SE
authors: Roh
authors: Yun Hwa
authors: YH
authors: Hong
authors: Dong Cheol
authors: DC
authors: Jang
authors: Jun
authors: J
authors: Kim
authors: Department of Physiology, Seoul National University College of Medicine, 28, Yeongeon-dong, Jongno-gu, Seoul 110-799, Korea. sangjkim@snu.ac.kr.
authors: Sang Jeong
authors: SJ
authors: Kim
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D020013:Calcium Signaling / Q000187:drug effects; D051242:Caveolin 1 / Q000378:metabolism*; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000494:pharmacology
chemical_list: D051242:Caveolin 1; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D054322:tat Gene Products, Human Immunodeficiency Virus