کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4323291 1291764 2006 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Differential Compartmentalization and Distinct Functions of GABAB Receptor Variants
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Differential Compartmentalization and Distinct Functions of GABAB Receptor Variants
چکیده انگلیسی

SummaryGABAB receptors are the G protein-coupled receptors for the main inhibitory neurotransmitter in the brain, γ-aminobutyric acid (GABA). Molecular diversity in the GABAB system arises from the GABAB1a and GABAB1b subunit isoforms that solely differ in their ectodomains by a pair of sushi repeats that is unique to GABAB1a. Using a combined genetic, physiological, and morphological approach, we now demonstrate that GABAB1 isoforms localize to distinct synaptic sites and convey separate functions in vivo. At hippocampal CA3-to-CA1 synapses, GABAB1a assembles heteroreceptors inhibiting glutamate release, while predominantly GABAB1b mediates postsynaptic inhibition. Electron microscopy reveals a synaptic distribution of GABAB1 isoforms that agrees with the observed functional differences. Transfected CA3 neurons selectively express GABAB1a in distal axons, suggesting that the sushi repeats, a conserved protein interaction motif, specify heteroreceptor localization. The constitutive absence of GABAB1a but not GABAB1b results in impaired synaptic plasticity and hippocampus-dependent memory, emphasizing molecular differences in synaptic GABAB functions.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 50, Issue 4, 18 May 2006, Pages 589–601
نویسندگان
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