117,291 research outputs found
Different internalization properties of the alpha1a and alpha1b-adrenergic receptor subytpes: the potential role of receptor interaction with beta-arrestins and AP50
No full textDirect interaction of ezrin with the alpha1b-adrenergic receptor regulates recycling of the internalized receptors
No full textOligomerization of the alpha1a- and alpha1b-adrenergic receptor subytpes: potential implications in receptor internalization
No full textStructural determinants involved in the activation and regulation of G protein-coupled receptors: lessons from the alpha1-adrenegic receptor subtypes
No full textThe alpha(1b)-adrenergic receptor subtype: Molecular properties and physiological implications
No full textThe aim of this review is to summarize some of the main findings from our laboratory as well as from others concerning the biochemical, molecular, and functional properties of the alpha1b-adrenergic receptor. Experimental and computational mutagenesis of the alpha1b-adrenergic receptor have been instrumental in elucidating some of the molecular mechanisms underlying receptor activation and receptor coupling to Gq. The knockout mouse model lacking the alpha1b-adrenergic receptor has highlighted the potential implication of this receptor subtype in variety of functions including the regulation of blood pressure, glucose homeostasis, and the rewarding response to drugs of abuse
Structural determinants involved in the activation and regulation of G protein-coupled receptors: lessons from the alpha1-adrenegic receptor subtypes
No full textThe aim of a large number of studies on G protein-coupled receptors was centered on understanding the structural basis of their main functional properties. Here, we will briefly review the results obtained on the alpha1-adrenergic receptor subtypes belonging to the rhodopsin-like family of receptors. These findings contribute, on the one hand, to further understand the molecular basis of adrenergic transmission and, on the other, to provide some generalities on the structure-functional relationship of G protein-coupled receptors
Paired activation of the two components within muscarinic M3 receptor dimers is required for recruitment of beta-arrestin-1 to the plasma membrane
No full text-Arrestins regulate the functioning of G protein-coupled
receptors in a variety of cellular processes including
receptor-mediated endocytosis and activation of signaling
molecules such as ERK. A key event in these
processes is the G protein-coupled receptor-mediated
recruitment of -arrestins to the plasma membrane.
However, despite extensive knowledge in this field, it is
still disputable whether activation of signaling pathways
via -arrestin recruitment entails paired activation
of receptor dimers. To address this question, we
investigated the ability of different muscarinic receptor
dimers to recruit -arrestin-1 using both co-immunoprecipitation
and fluorescence microscopy in COS-7 cells.
Experimentally, we first made use of a mutated muscarinic
M3 receptor, which is deleted in most of the third
intracellular loop (M3-short). Although still capable of
activating phospholipase C, this receptor loses almost
completely the ability to recruit -arrestin-1 following
carbachol stimulation in COS-7 cells. Subsequently, M3-
short was co-expressed with the M3 receptor. Under
these conditions, the M3/M3-short heterodimer could not
recruit -arrestin-1 to the plasma membrane, even
though the control M3/M3 homodimer could. We next
tested the ability of chimeric adrenergic muscarinic
2/M3 and M3/2 heterodimeric receptors to co-immunoprecipitate
with -arrestin-1 following stimulation with
adrenergic and muscarinic agonists. -Arrestin-1 co-immunoprecipitation
could be induced only when carbachol
or clonidine were given together and not when the
two agonists were supplied separately. Finally, we
tested the reciprocal influence that each receptor may
exert on the M2/M3 heterodimer to recruit -arrestin-1.
Remarkably, we observed that M2/M3 heterodimers recruit
significantly greater amounts of -arrestin-1 than
their respective M3/M3 or M2/M2 homodimers. Altogether,
these findings provide strong evidence in favor
of the view that binding of -arrestin-1 to muscarinic M3
receptors requires paired stimulation of two receptor
components within the same receptor dimer
Paired activation of two components within muscarinic M3 receptor dimers is required for recruitment of beta-arrestin-1 to the plasma membrane
No full textPaired activation of the two components within muscarinic M3 receptor dimers is required for recruitment of beta-arrestin-1 to the plasma membrane
No full textbeta-Arrestins regulate the functioning of G protein-coupled receptors in a variety of cellular processes including receptor-mediated endocytosis and activation of signaling molecules such as ERK. A key event in these processes is the G protein-coupled receptor-mediated recruitment of beta-arrestins to the plasma membrane. However, despite extensive knowledge in this field, it is still disputable whether activation of signaling pathways via beta-arrestin recruitment entails paired activation of receptor dimers. To address this question, we investigated the ability of different muscarinic receptor dimers to recruit beta-arrestin-1 using both co-immunoprecipitation and fluorescence microscopy in COS-7 cells. Experimentally, we first made use of a mutated muscarinic M(3) receptor, which is deleted in most of the third intracellular loop (M(3)-short). Although still capable of activating phospholipase C, this receptor loses almost completely the ability to recruit beta-arrestin-1 following carbachol stimulation in COS-7 cells. Subsequently, M(3)-short was co-expressed with the M(3) receptor. Under these conditions, the M(3)/M(3)-short heterodimer could not recruit beta-arrestin-1 to the plasma membrane, even though the control M(3)/M(3) homodimer could. We next tested the ability of chimeric adrenergic muscarinic alpha(2)/M(3) and M(3)/alpha(2) heterodimeric receptors to co-immunoprecipitate with beta-arrestin-1 following stimulation with adrenergic and muscarinic agonists. beta-Arrestin-1 co-immunoprecipitation could be induced only when carbachol or clonidine were given together and not when the two agonists were supplied separately. Finally, we tested the reciprocal influence that each receptor may exert on the M(2)/M(3) heterodimer to recruit beta-arrestin-1. Remarkably, we observed that M(2)/M(3) heterodimers recruit significantly greater amounts of beta-arrestin-1 than their respective M(3)/M(3) or M(2)/M(2) homodimers. Altogether, these findings provide strong evidence in favor of the view that binding of beta-arrestin-1 to muscarinic M(3) receptors requires paired stimulation of two receptor components within the same receptor dimer
- …
