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Optical control of cell-surface and endomembrane-exclusive ß-adrenergic receptor signaling.
Thotamune, Waruna; Ubeysinghe, Sithurandi; Shrestha, Kendra K; Mostafa, Mahmoud Elhusseiny; Young, Michael C; Karunarathne, Ajith.
Afiliação
  • Thotamune W; Department of Chemistry, Saint Louis University, Saint Louis, Missouri, USA.
  • Ubeysinghe S; Department of Chemistry, Saint Louis University, Saint Louis, Missouri, USA.
  • Shrestha KK; Department of Chemistry and Biochemistry, School of Green Chemistry and Engineering, The University of Toledo, Toledo, Ohio, USA.
  • Mostafa ME; Department of Chemistry, Saint Louis University, Saint Louis, Missouri, USA.
  • Young MC; Department of Chemistry and Biochemistry, School of Green Chemistry and Engineering, The University of Toledo, Toledo, Ohio, USA. Electronic address: Michael.Young8@UToledo.edu.
  • Karunarathne A; Department of Chemistry, Saint Louis University, Saint Louis, Missouri, USA. Electronic address: wkarunarathne@slu.edu.
J Biol Chem ; 300(7): 107481, 2024 Jul.
Article em En | MEDLINE | ID: mdl-38901558
ABSTRACT
Beta-adrenergic receptors (ßARs) are G protein-coupled receptors (GPCRs) that mediate catecholamine hormone-induced stress responses, such as elevation of heart rate. Besides those that are plasma membrane-bound, endomembrane ßARs are also signaling competent. Dysregulation of ßAR pathways underlies severe pathological conditions. Emerging evidence indicates pathological molecular signatures in deeper endomembrane ßARs signaling, likely contributing to conditions such as cardiomyocyte hypertrophy and apoptosis. However, the lack of approaches to control endomembrane ß1ARs has impeded linking signaling with pathology. Informed by the ß1AR-catecholamine interactions, we engineered an efficient photolabile proligand (OptoIso) to trigger ßAR signaling exclusively in endomembrane regions using blue light stimulation. Not only does OptoIso undergo blue light deprotection in seconds, but also efficiently enters cells and allows examination of G protein heterotrimer activation exclusively at endomembranes. OptoIso also allows optical activation of plasma membrane ßAR signaling in selected single cells with native fidelity, which can be reversed by terminating blue light. Thus, OptoIso will be a valuable experimental tool to elicit spatial and temporal control of ßAR signaling in user-defined endomembrane or plasma membrane regions in unmodified cells with native fidelity.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Membrana Celular / Receptores Adrenérgicos beta 1 Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Membrana Celular / Receptores Adrenérgicos beta 1 Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article