Abstract
The electron-dense spherical granules found in the perinuclear region of atrial myocytes store and release both proatrial and probrain natriuretic peptides (proANP and proBNP, respectively). Mature ANP and BNP produce vasodilation and natriuresis and inhibit the renin-angiotensin and sympathetic nervous systems. Although neither ANP nor BNP is a-amidated, Peptidylglycine a-Amidating Monooxygenase (PAM), an integral membrane enzyme known to catalyze the a-amidation of peptidylglycine precursors, is the major atrial granule membrane protein. Selective deletion of PAM from cardiomyocytes impairs their ability to store proANP, resulting in an increase in proANP secretion. Exogenous expression of active or inactive PAM protein restores the ability of atrial myocytes to store proANP, leading to the suggestion that PAM functions as a cargo receptor for newly synthesized proANP.
Highlights
Neither atrial natriuretic peptide (ANP) nor brain natriuretic peptide (BNP) is a-amidated, Peptidylglycine a-Amidating Monooxygenase (PAM), an integral membrane enzyme known to catalyze the a-amidation of peptidylglycine precursors, is the major atrial granule membrane protein
Exogenous expression of active or inactive PAM protein restores the ability of atrial myocytes to store proANP, leading to the suggestion that PAM functions as a cargo receptor for newly synthesized proANP
The electron-dense spherical granules found in atrial myocytes are one of the most obvious features distinguishing these cells from ventricular myocytes (Figure 1A)
Summary
Commentary on: Peptidylglycine α-amidating Monooxygenase is Required for Atrial Secretory Granule Formation. Emil Daniel Bartels, MD, PHD1,2, Jens Peter Gøtze, MD, DSMC1,3, Richard E. PHD4,5 1Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark 2Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark 3Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark 4Department of Neuroscience, University of Connecticut Health Center, Farmington CT USA 5Department of Molecular Biology & Biochemistry, University of Connecticut Health Center, Farmington CT USA
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