کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5816215 | 1115562 | 2009 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Importance of the C-terminus of the human 5-HT3A receptor subunit
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
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چکیده انگلیسی
Amongst the family members of Cys-loop LGICs, the atypical ability of the 5-HT3A subunit to form functional homomeric receptors allowed a direct investigation of the role of the C-terminus. Deletion of the three C-terminal amino acids (ÎGln453-ÎTyr454-ÎAla455) from the h5-HT3A subunit prevented formation of a specific radioligand binding site as well as expression within the cell membrane. Removal of merely the C-terminal residue (ÎAla455) reduced specific radioligand binding (to 4 ± 1% relative to the wild-type; cells grown at 37 °C) and also cell membrane expression; these reductions were less evident when the ÎAla455 expressing cells were grown at 27 °C (specific radioligand binding levels 27 ± 5% relative to wild-type also grown at 27 °C). Mutation of the h5-HT3A C-terminal amino acid, alanine, for either glycine (Ala455Gly), valine (Ala455Val) or leucine (Ala455Leu) reduced specific radioligand binding levels by 24 ± 23%, 32 ± 12% and 88 ± 1%, respectively; the latter mutant also displaying reduced membrane expression. In contrast, mutation to alanine of the two amino acids preceding the C-terminal alanine (Gln453Ala and Tyr454Ala) had no detrimental effects on specific radioligand binding or cell membrane expression levels. The present study demonstrates an important role for the C-terminus in the formation of the functional h5-HT3A receptor. The partial restoration of 5-HT3 receptor binding and cell membrane expression when cells expressing C-terminal mutant 5-HT3A subunits were grown at a lower temperature (27 °C) suggests that the C-terminus stabilises the 5-HT3 receptor allowing subunit folding and subsequent maturation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 56, Issue 1, January 2009, Pages 292-302
Journal: Neuropharmacology - Volume 56, Issue 1, January 2009, Pages 292-302
نویسندگان
Amy S. Butler, Sarah A. Lindesay, Terri J. Dover, Matthew D. Kennedy, Valerie B. Patchell, Barry A. Levine, Anthony G. Hope, Nicholas M. Barnes,