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-Adrenergic Receptor Trafficking in Adult Cardiocytes by MAP4 Decoration of Microtubules
1 Gazes Cardiac Research Institute, Medical University of South Carolina, Charleston, SC, USA
* To whom correspondence should be addressed. E-mail: cooperge{at}musc.edu.
Decreased 
-adrenergic receptor (-AR) number occurs both in animal models of cardiac hypertrophy and failure and in patients. -AR recycling is an important mechanism for the -AR resensitization that maintains a normal complement of cell surface -ARs. We have shown that 1) in severe pressure overload cardiac hypertrophy there is extensive microtubule-associated protein 4 (MAP4) decoration of a dense microtubule network, and 2) MAP4 microtubule decoration inhibits muscarinic acetylcholine receptor recycling in neuroblastoma cells. We asked here whether MAP4 microtubule decoration inhibits -AR recycling in adult cardiocytes. [3H]CGP-12177 was used as a -AR ligand, and feline cardiocytes were isolated and infected with adenovirus containing MAP4 (AdMAP4) or -galactosidase (Ad-gal) cDNA. MAP4 decorated the microtubules extensively only in AdMAP4 cardiocytes. -AR agonist exposure reduced cell surface -AR number comparably in AdMAP4 and Ad-gal cardiocytes; however, after agonist withdrawal, cell surface -AR number recovered to 78.4 ± 2.9% of the pre-treatment value in Ad-gal cardiocytes but only to 56.8 ± 1.4% in AdMAP4 cardiocytes (P < 0.01). This result was confirmed in cardiocytes isolated from transgenic mice having cardiac-restricted MAP4 overexpression. In functional terms of cAMP generation, -AR agonist responsiveness of AdMAP4 cells was 47% less than that of Ad-gal cells. We conclude that MAP4 microtubule decoration interferes with -AR recycling and that this may be one mechanism for -AR downregulation in heart failure.
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