کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2493885 1115533 2011 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The intra-molecular activation mechanisms of the dimeric metabotropic glutamate receptor 1 differ depending on the type of G proteins
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
The intra-molecular activation mechanisms of the dimeric metabotropic glutamate receptor 1 differ depending on the type of G proteins
چکیده انگلیسی

Metabotropic glutamate receptor 1 (mGlu1) functions as a homodimer and activates not only the Gq but also the Gi/o and Gs pathways. Because of the dimeric configuration, different pathways could be activated either through the glutamate-bound subunit (cis-activation) and/or the other one (trans-activation). We here examined whether the intra-molecular activation mechanisms in the mGlu1 differ depending on the type of coupling G proteins, using various combinations of mGlu1 constructs that lack glutamate binding and/or G-protein coupling. The cis- or trans-activation alone was confirmed to trigger the Gq-coupled intracellular Ca2+ transient. In contrast, the Gi/o-coupled G protein-dependent inward rectifying potassium (GIRK) channels were not activated either through the cis- or trans-activation alone. When one subunit of dimeric mGlu1 lacked the G-protein coupling, a significant decrease in the glutamate-induced GIRK current density was also observed. As the G protein-coupling-deficient subunit did not decrease the cell surface expression of mGlu1 and the Gq-coupled Ca2+ transient, it was suggested that the coupling deficiency in one subunit of mGlu1 attenuates the Gi/o but not Gq coupling. In conclusion, multiple G-protein signaling was differentially activated by different intra-molecular activation mechanisms of the dimeric mGlu1.


► We investigated the activation mechanisms of G proteins by dimeric mGlu1.
► We examined the effects of one G protein-coupling-deficient subunit of dimer.
► Activation of Gq pathway was not affected by the coupling-deficient subunit.
► In clear contrast, activation of Gi pathway was significantly attenuated.
► Activation mechanisms by mGlu1 dimer differ depending on the types of G proteins.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 61, Issue 4, September 2011, Pages 832–841
نویسندگان
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