Structural Rearrangement and Functional Regulation of the Metabotropic Glutamate Receptor
In this chapter, we focus chiefly on our studies of the regulatory mechanisms and structural rearrangements that affect signaling via the metabotropic glutamate receptor (mGluR), and we also introduce related studies by other groups investigating the dyna
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Structural Rearrangement and Functional Regulation of the Metabotropic Glutamate Receptor
Y. Kubo . M. Tateyama
1
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334
2
Sensitivity to Polyvalent Cations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334
3
Crystal Structure Analysis—Dimeric Structure and the Venus Flytrap Module . . . . . . . . . . . . . . . 335
4
Crystal Structure Analysis—Binding Sites for Polyvalent Cations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 336
5
Structural Rearrangement of the Cytoplasmic Region of mGluR1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 336
6
Factors Regulating the Switching Among Multiple Signaling Pathways 1—Ligand Type . . . . . . 338
7
Factors Regulating the Switching Among Multiple Signaling Pathways 2—Differences Between Splice Variants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339
8
Factors Regulating the Switching Among Multiple Signaling Pathways 3—Effects of Cytoplasmic-Binding Protein . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 340
9
Physiological Significance of Gd3+ Sensing Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341
10 Future Directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342
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2009 Springer Science+Business Media, LLC.
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Structural rearrangement and functional regulation of the metabotropic glutamate receptor
Abstract: In this chapter, we focus chiefly on our studies of the regulatory mechanisms and structural rearrangements that affect signaling via the metabotropic glutamate receptor (mGluR), and we also introduce related studies by other groups investigating the dynamic aspects of mGluR1. The topics covered include (1) the sensitivity of mGluR1 to polyvalent cations, (2) fluorescence resonance energy transfer analysis of the structural rearrangement of the cytoplasmic region of mGluR1, and (3) switching of mGluR1 signaling among multiple pathways, depending upon the ligand type, the splice variation of the C-terminal structure, and the presence of cytoplasmic-binding proteins. List of Abbreviations: Cao2+, extracellular calcium; Ca2+ i , intracellular calcium; CFP, cyan fluorescent protein; FRET, fluorescence resonance energy transfer; Gdo3+, extracellular gadorinium; LTD, long-term depression; LTP, long-term potentiation; mGluR, metabotropic glutamate receptor; 7TMD, seven transmembrane domain; TIRF, total internal reflection; VFTM, venus flytrap module; YFP, yellow fluorescent protein
1 Introduction The ex
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