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Proteomics of Dense Core Secretory Vesicles Reveal Distinct Protein Categories for Secretion of Neuroeffectors for Cell−Cell Communication

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Skaggs School of Pharmacy and Pharmaceutical Sciences, Departments of Pediatrics, Cellular and Molecular Medicine, Pathology, Medicine, and Neurosciences, School of Medicine, University of California, San Diego, La Jolla, California 92093
* To whom correspondence should be addressed. Vivian Hook, Ph.D., School of Pharmacy, Univ. of Calif, San Diego, 9500 Gilman Dr. MC 0744, La Jolla, CA 92093, phone (858) 822-6682, e-mail: [email protected]
†The first two authors contributed equal and significant efforts to this study.
‡Skaggs School of Pharmacy and Pharmaceutical Sciences.
§Departments of Pediatrics and Cellular and Molecular Medicine.
∥Department of Pathology.
⊥Department of Medicine.
#Department of Neurosciences and Medicine.
Cite this: J. Proteome Res. 2010, 9, 10, 5002–5024
Publication Date (Web):August 9, 2010
https://doi.org/10.1021/pr1003104
Copyright © 2010 American Chemical Society

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    Abstract

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    Regulated secretion of neurotransmitters and neurohumoral factors from dense core secretory vesicles provides essential neuroeffectors for cell−cell communication in the nervous and endocrine systems. This study provides comprehensive proteomic characterization of the categories of proteins in chromaffin dense core secretory vesicles that participate in cell−cell communication from the adrenal medulla. Proteomic studies were conducted by nano-HPLC Chip MS/MS tandem mass spectrometry. Results demonstrate that these secretory vesicles contain proteins of distinct functional categories consisting of neuropeptides and neurohumoral factors, protease systems, neurotransmitter enzymes and transporters, receptors, enzymes for biochemical processes, reduction/oxidation regulation, ATPases, protein folding, lipid biochemistry, signal transduction, exocytosis, calcium regulation, as well as structural and cell adhesion proteins. The secretory vesicle proteomic data identified 371 proteins in the soluble fraction and 384 membrane proteins, for a total of 686 distinct secretory vesicle proteins. Notably, these proteomic analyses illustrate the presence of several neurological disease-related proteins in these secretory vesicles, including huntingtin interacting protein, cystatin C, ataxin 7, and prion protein. Overall, these findings demonstrate that multiple protein categories participate in dense core secretory vesicles for production, storage, and secretion of bioactive neuroeffectors for cell−cell communication in health and disease.

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