کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10956909 | 1099463 | 2005 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The epilepsy mutation, γ2(R43Q) disrupts a highly conserved inter-subunit contact site, perturbing the biogenesis of GABAA receptors
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: The epilepsy mutation, γ2(R43Q) disrupts a highly conserved inter-subunit contact site, perturbing the biogenesis of GABAA receptors The epilepsy mutation, γ2(R43Q) disrupts a highly conserved inter-subunit contact site, perturbing the biogenesis of GABAA receptors](/preview/png/10956909.png)
چکیده انگلیسی
Given the association of a γ2 mutation (R43Q) with epilepsy and the reduced cell surface expression of mutant receptors, we investigated a role for this residue in α1β2γ2 receptor assembly when present in each subunit. Regardless of which subunit contained the mutation, mutant GABAA receptors assembled poorly into functional cell surface receptors. The low level of functional expression gives rise to reduced GABA EC50s (α1(R43Q)β2γ2 and α1β2(R43Q)γ2) or reduced benzodiazepine potentiation of GABA-evoked currents (α1β2γ2(R43Q)). We determined that a 15-residue peptide surrounding R43 is capable of subunit binding, with a profile that reflected the orientation of subunits in the pentameric receptor. Subunit binding is perturbed when the R43Q mutation is present suggesting that this residue is critical for the formation of inter-subunit contacts at (+) interfaces of GABAA subunits. Rather than being excluded from receptors, γ2(R43Q) may form non-productive subunit interactions leading to a dominant negative effect on other receptor subtypes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Neuroscience - Volume 29, Issue 1, May 2005, Pages 120-127
Journal: Molecular and Cellular Neuroscience - Volume 29, Issue 1, May 2005, Pages 120-127
نویسندگان
Tim G. Hales, Haiyan Tang, Karen A. Bollan, Sara J. Johnson, Dale P. King, Neil A. McDonald, Aixin Cheng, Christopher N. Connolly,