Timothy Angelotti MD, PhD

Publication Details

  • Regulation of G-Protein Coupled Receptor Traffic by an Evolutionary Conserved Hydrophobic Signal TRAFFIC Angelotti, T., Daunt, D., Shcherbakova, O. G., Kobilka, B., Hurt, C. M. 2010; 11 (4): 560-578

    Abstract:

    Plasma membrane (PM) expression of G-protein coupled receptors (GPCRs) is required for activation by extracellular ligands; however, mechanisms that regulate PM expression of GPCRs are poorly understood. For some GPCRs, such as alpha2c-adrenergic receptors (alpha(2c)-ARs), heterologous expression in non-native cells results in limited PM expression and extensive endoplasmic reticulum (ER) retention. Recently, ER export/retentions signals have been proposed to regulate cellular trafficking of several GPCRs. By utilizing a chimeric alpha(2a)/alpha(2c)-AR strategy, we identified an evolutionary conserved hydrophobic sequence (ALAAALAAAAA) in the extracellular amino terminal region that is responsible in part for alpha(2c)-AR subtype-specific trafficking. To our knowledge, this is the first luminal ER retention signal reported for a GPCR. Removal or disruption of the ER retention signal dramatically increased PM expression and decreased ER retention. Conversely, transplantation of this hydrophobic sequence into alpha(2a)-ARs reduced their PM expression and increased ER retention. This evolutionary conserved hydrophobic trafficking signal within alpha(2c)-ARs serves as a regulator of GPCR trafficking.

    View details for DOI 10.1111/j.1600-0854.2010.01033.x

    View details for Web of Science ID 000275530700012

    View details for PubMedID 20059747

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