Abstract：
:This study examined whether the conserved arginine cluster present within the 29-amino acid insert of the long form of the D₂ dopamine receptor (D2L-R) confers its predominant intracellular localization. We hypothesized that the conserved arginine cluster (RRR) located within the insert could act as an RXR-type endoplasmic reticulum (ER) retention signal. Arginine residues (R) within the cluster at positions 267, 268, and 269 were charge-reserved to glutamic acids (E), either individually or in clusters, thus generating single, double, and triple D2L-R mutants. Through analyses of cellular localization by confocal microscopy and enzyme-linked immunosorbent assay (ELISA), radioligand binding assay, bioluminescence resonance energy transfer (BRET²) β-arrestin 2 (βarr2) recruitment assay, and cAMP signaling, it was revealed that charge reversal of the R residues at all three positions within the motif impaired their colocalization with ER marker calnexin and led to significantly improved cell surface expression. Additionally, these data demonstrate that an R to glutamic acid (E) substitution at position 2 within the RXR motif is not functionally permissible. Furthermore, all generated D2L-R mutants preserved their functional integrity regarding ligand binding, agonist-induced βarr2 recruitment and Gαi-mediated signaling. In summary, our results show that the conserved arginine cluster within the 29-amino acid insert of third cytoplasmic loop (IC3) of the D2L-R appears to be the ER retention signal.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Kubale V,Blagotinšek K,Nøhr J,Eidne KA,Vrecl Mdoi
10.3390/ijms17071152subject
Has Abstractpub_date
2016-07-19 00:00:00issue
7issn
1422-0067pii
ijms17071152journal_volume
17pub_type
杂志文章abstract：:Lung squamous cell carcinoma (LUSC) has a poor prognosis, in part due to poor therapeutic response and limited therapeutic alternatives. Lichens are symbiotic organisms, producing a variety of substances with multiple biological activities. (+)-Usnic acid, an important biologically active metabolite of lichens, has be...
journal_title：International journal of molecular sciences
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更新日期：2020-01-29 00:00:00
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journal_title：International journal of molecular sciences
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更新日期：2018-08-06 00:00:00
abstract：:Nerve growth factor (NGF) promotes the survival and differentiation of neurons. NGF is initially synthesized as a precursor, proNGF, which is the predominant form in the central nervous system. NGF and proNGF bind to TrkA/p75NTR to mediate cell survival and to sortilin/p75NTR to promote apoptosis. The ratio of TrkA to...
journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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更新日期：2019-02-10 00:00:00
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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journal_title：International journal of molecular sciences
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更新日期：2018-10-30 00:00:00
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journal_title：International journal of molecular sciences
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更新日期：2016-08-31 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms141223545
更新日期：2013-12-02 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21165605
更新日期：2020-08-05 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms20020273
更新日期：2019-01-11 00:00:00
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journal_title：International journal of molecular sciences
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更新日期：2019-02-14 00:00:00
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journal_title：International journal of molecular sciences
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更新日期：2020-08-09 00:00:00
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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更新日期：2010-06-09 00:00:00
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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更新日期：2012-01-01 00:00:00
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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更新日期：2020-02-04 00:00:00
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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更新日期：2019-05-02 00:00:00
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journal_title：International journal of molecular sciences
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更新日期：2020-04-27 00:00:00
