Refugee Receptors Switch Sides

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Science  26 Mar 2010:
Vol. 327, Issue 5973, pp. 1586-1587
DOI: 10.1126/science.1188538

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Human heart muscle cells (cardiomyocytes) express two different types of β adrenergic receptor: β1AR and β2AR. Both respond to the same hormones and couple to the same biochemical signaling effectors, yet they elicit different cellular responses. On page 1653 of this issue, Nikolaev et al. (1) show that β1ARs are widely distributed at the plasma membrane (crest) of a normal cardiomyocyte, whereas β2ARs localize to transverse-tubular (T-tubule) regions at the cell surface, thus segregating their signaling. Remarkably, failing cardiomyocytes exhibit membrane remodeling that disrupts compartmentalization of βARs. This may be a primary mechanism for the pathological effects of βAR signaling in heart failure and disease.