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Novel paradigms governing β 1 ‐adrenergic receptor trafficking in primary adult rat cardiac myocytes
Author(s) -
Nooh Mohammed Mostafa,
Mancarella Salvatore M.,
Bahouth Suleiman W.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.685.9
Subject(s) - sarcolemma , myocyte , endosome , microbiology and biotechnology , chemistry , internalization , sarcomere , receptor , medicine , agonist , endocrinology , biology , biochemistry
Background and Purpose The β 1 ‐adrenergic receptor (β 1 ‐AR) is a major cardiac G protein‐coupled receptor (GPCR), which mediates cardiac actions of catecholamines and is involved in genesis and treatment of numerous cardiovascular disorders. Catecholamines induce the internalization of the β 1 ‐AR into endosomes and their removal promotes the recycling of endosomal β 1 ‐AR back to the plasma membrane (PM). Experimental Approach Trafficking of the β 1 ‐AR and its regulation was determined by confocal microscopy in primary adult rat ventricular myocytes (ARVM), which are terminally differentiated myocytes with unique structures such as t‐tubules and contractile sarcomeres. Key Results In unstimulated ARVM, the fluorescently labeled wild type (WT) β 1 ‐AR was expressed on the external membranes (the sarcolemma) of cardiomyocytes. Exposing ARVM to isoprenaline promoted the translocation of surface β 1 ‐AR into small (~225–250 nm) regularly spaced internal punctate structures that overlapped with puncta stained by Di‐8‐ANEPPS, a t‐tubule‐specific dye. Replacing the β‐agonist with a β‐blocker such as alprenolol, induced the recycling of the WT β 1 ‐AR from t‐tubules back to the PM. This step was dependent on two previously identified β 1 ‐AR barcodes, namely the type‐1 PDZ binding motif (PBM) and Ser 312 of the β 1 ‐AR, which is phosphorylated by the PBM anchored PKA‐AKAP5‐SAP97 complex. Conclusions and Implications We present data to show that translocation of the β 1 ‐AR from t‐tubules back to the PM in ARVM was mediated by a novel sorting mechanism. These findings might explain unique aspects of cardiac β 1 ‐AR signaling under normal or pathological conditions. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .