title: Proteomic analysis of rat atrial secretory granules: a platform for testable hypotheses.
abstract: The recent development of powerful proteomic tools has enabled investigators to directly examine the population of proteins present in defined biological systems. We report here the first proteomic analysis of atrial secretory granules. Approximately 100 distinct protein components of the atrial secretory granule proteome were detected using subcellular fractionation and one-dimensional SDS-PAGE in conjunction with peptide mass fingerprinting by MALDI-TOF mass spectrometry. Of this number, 61 proteins were clearly identified by high probability data matches and repeated observation. The majority of the proteome was found to be membrane-associated with the most prominent proteins being peptidylglycine alpha-amidating monooxygenase (PAM) and pro-atrial natriuretic peptide (pro-ANP). This proteomic analysis of the rat atrium secretory granule produced an assembly of proteins with a diverse array of reported functions. The identified proteins fall into seven functional categories: (1) granular transport, docking and fusion; (2) signal transduction; (3) calcium-binding/calcium-dependent; (4) cellular architecture/chaperoning; (5) peptide/protein processing; (6) hormone; (7) proton transport. The novel finding of several protein processing enzymes and signal transduction proteins offer new perspectives on how pro-ANP is stored and processed to ANP during release. Accordingly, defining the proteome of the atrial secretory granule provides a framework for the development of new hypotheses that address key mechanisms governing granule function and ANP secretion.
authors.affiliation: Department of Anatomy, Physiology and Genetics, Center for Medical Genetics and Proteomics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Muth
authors.forename: William J
authors.initials: WJ
authors.lastname: Driscoll
authors.forename: Alexi
authors.initials: A
authors.lastname: Smalstig
authors.forename: Gertrud
authors.initials: G
authors.lastname: Goping
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Mueller
mesh_terms: D000818:Animals; D005260:Female; D006325:Heart Atria / Q000378:metabolism*; D010449:Peptide Mapping; D020543:Proteome; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D022142:Secretory Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D015398:Signal Transduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013347:Subcellular Fractions
chemical_list: D020543:Proteome