The protein architecture of human secretory vesicles reveals differential regulation of signaling molecule secretion by protein kinases.
Secretory vesicles are required for release of chemical messengers to mediate intercellular signaling among human biological systems. It is necessary to define the organization of the protein architecture of the 'human' dense core secretory vesicles (DCSV) to understand mechanisms for secretion of signaling molecules essential for cellular regulatory processes. This study, therefore, conducted extensive quantitative proteomics and systems biology analyses of human DCSV purified from human pheochromocytoma. Over 600 human DCSV proteins were identified with quantitative evaluation of over 300 proteins, revealing that most proteins participate in producing peptide hormones and neurotransmitters, enzymes, and the secretory machinery. Systems biology analyses provided a model of interacting DCSV proteins, generating hypotheses for differential intracellular protein kinases A and C signaling pathways. Activation of cellular PKA and PKC pathways resulted in differential secretion of neuropeptides, catecholamines, and β-amyloid of Alzheimer's disease for mediating cell-cell communication. This is the first study to define a model of the protein architecture of human DCSV for human disease and health.
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA. stevenjbark@central.uh.edu
Steven J
SJ
Bark
Jill
J
Wegrzyn
Laurent
L
Taupenot
Michael
M
Ziegler
Daniel T
DT
O'Connor
Qi
Q
Ma
Michael
M
Smoot
Trey
T
Ideker
Vivian
V
Hook
D006801:Humans; D008958:Models, Molecular; D011494:Protein Kinases / Q000378:metabolism*; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D040901:Proteomics; D015398:Signal Transduction
D011506:Proteins; D011494:Protein Kinases