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Post‐endocytotic trafficking of ETB receptors in cardiomyocytes: effects of pressure‐overload hypertrophy on their subcellular distribution.
Author(s) -
MERLEN Clemence,
FARHAT Nada,
Villeneuve Louis R.,
Gillis MarcAntoine,
Thorin Eric,
Allen Bruce G.
Publication year - 2010
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.24.1_supplement.857.4
Subject(s) - receptor , immunofluorescence , pressure overload , microbiology and biotechnology , muscle hypertrophy , medicine , myocyte , endocrinology , chemistry , biology , cardiac hypertrophy , antibody , immunology
Endothelins are implicated in both cardiac function and pathophysiology via their actions on ETA (selective for ET‐1>>ET‐3) and ETB (non selective) receptors. To date, the cellular signaling evoked by ET‐1 has been studied by activating receptors at the cell surface. However, ETB are primarily located on the nuclear membrane in adult cardiac ventricular myocytes (ACVMs). The present study was to determine the origin of these receptors. In ACVMs, which express ETA and ETB, fluorescently‐labeled ET‐1 was internalized and localized to lysosomes plus perinuclear structures. ET‐3 was transported soley to lysosomes. In rat aortic endothelial cells, which express ETB, endocytosed ET‐1 and ET‐3 were transported to lysosomes. To determine if the subcellular distribution of ETRs was altered during hypertrophy, mice were subjected to transverse aortic constriction (TAC) for 7 days and the distribution of ETRs examined by immunocytofluorescence. Whereas ETB immunofluorescence was associated with the nuclear membrane in sham animals, additional perinuclear staining was observed in TAC hearts. The distribution of ETA immunofluorescence was unaffected. Hence, localization of ETB to the nuclear membrane is not a result of post‐endocytotic ligand/receptor complex trafficking and the subcellular distribution, and possibly trafficking, of ETB is altered during hypertrophy. (Supported by the CIHR, FICM and HSFC)