This Article Full Text Full Text (PDF) Data Supplement Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Baertschi, A. J. Articles by Roatti, A. Search for Related Content PubMed PubMed Citation Articles by Baertschi, A. J. Articles by Roatti, A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL Related Collections Other myocardial biology Physiological and pathological control of gene expression

(Circulation Research. 2001;89:e23.)
© 2001 American Heart Association, Inc.

UltraRapid Communication

Acid Prohormone Sequence Determines Size, Shape, and Docking of Secretory Vesicles in Atrial Myocytes

Alex J. Baertschi, Dominique Monnier, Uta Schmidt, Edwin S. Levitan, Stanislas Fakan, Angela Roatti

From the Departments of Physiology (A.J.B., U.S., A.R.) and Pharmacology (D.M.), Centre Médical Universitaire, University of Geneva, Geneva, Switzerland; Department of Pharmacology (E.S.L.), University of Pittsburgh, Pittsburgh, Pa; and Center of Electron Microscopy (S.F.), University of Lausanne, Lausanne, Switzerland.

Correspondence to Dr Alex J. Baertschi, Physiology, CMU, 1 Rue Michel-Servet, 1211 Geneva 4, Switzerland. E-mail alex.baertschi{at}medecine.unige.ch

Abstract— How vesicles are born in the trans-Golgi network and reach their docking sites at the plasma membrane is still largely unknown and is investigated in the present study on live, primary cultured atrial cardiomyocytes. Secretory vesicles (n=422) are visualized by expressing fusion proteins of proatrial natriuretic peptide (proANP) and green fluorescent protein. Myocytes expressing fusion proteins with intact proANP display two populations of fluorescent vesicles with apparent diameters of 120 and 175 nm, moving at a top velocity of 0.3 µm/s. The number of docked vesicles is significantly correlated with the number of mobile vesicles (r=0.71, P<0.0005). The deletion of the acidic N-terminal proANP[1-44] or point mutations (glu_23,24gln_23,24) change size and shape—but not velocity—of the vesicles, and, strikingly, abolish their docking at the plasma membrane. The shapes thus change from spheres to larger, irregular floppy bags or vesicle trains. Deletion of the C-terminal proANP[45-127], where the ANP and its disulfide bond reside, does not change size, shape, docking, or velocity of the mobile vesicles. The N-terminal acid calcium-binding sequence of proANP is known to cause protein aggregation at the high calcium concentration prevailing in the trans-Golgi network. Therefore, these results indicate that amino acid residues favoring cargo aggregation are critically important in shaping the secretory vesicles and determining their fate—docking or not docking—at the plasma membrane. The full text of this article is available at http://www.circresaha.org.

Key Words: atrium • enhanced green fluorescent protein • in vivo imaging • proatrial natriuretic peptide • secretory vesicles