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Competitive interaction of Seven in absentia homolog‐1A and Ca 2+ /calmodulin with the cytoplasmic tail of group 1 metabotropic glutamate receptors
Author(s) -
Ishikawa Kenji,
Nash S. Russell,
Nishimune Atsushi,
Neki Akio,
Kaneko Satoshi,
Nakanishi Shigetada
Publication year - 1999
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1046/j.1365-2443.1999.00269.x
Subject(s) - biology , calmodulin , metabotropic receptor , metabotropic glutamate receptor , glutamate receptor , receptor , biochemistry , enzyme
Background Group 1 metabotropic glutamate receptors (mGluR1 and mGluR5) are coupled to inositol trisphosphate/Ca 2+ signaling via G proteins and play an important role in excitatory synaptic transmission. To explore the regulation of group 1 mGluR function, we applied the yeast two‐hybrid system using the intracellular carboxy‐terminal domain of group 1 mGluRs (group 1 ct‐mGluRs) and attempted to identify novel protein–protein interactions of group 1 mGluRs. Results The two‐hybrid screening revealed a specific interaction between group 1 ct‐mGluRs and Siah‐1A, the mammalian homolog of Drosophila seven in absentia which is involved in photoreceptor cell differentiation via the ubiquitin/proteasome‐dependent mechanism. This interaction occurs within a homologous 27–28 amino acid stretch within group 1 ct‐mGluRs and requires the latter two‐thirds of Siah‐1A. Following coexpression in COS‐7 cells, myc‐tagged Siah‐1A was coimmunoprecipitated with the flag‐tagged ct‐mGluR1 by anti‐flag antibody. Furthermore, in vitro binding revealed that Siah‐1A and Ca 2+ /calmodulin (CaM) binding sites overlap, such that Siah‐1A binding is competitively inhibited by CaM in a Ca 2+ ‐dependent manner. Conclusions The results demonstrate a direct interaction between group 1 mGluRs and Siah‐1A and suggest a novel modulatory mechanism mediated by a competitive interaction between Ca 2+ /CaM and Siah‐1A.