title: Quantitative immunofluorescence mapping reveals little functional coclustering of proteins within platelet α-granules.
abstract: Platelets are small anucleate blood cells that aggregate to seal leaks at sites of vascular injury and are important in the pathology of atherosclerosis, acute coronary syndromes, rheumatoid arthritis, cancer, and the regulation of angiogenesis. In all cases, platelet aggregation requires release of stored proteins from α-granules. However, how proteins with potentially antagonistic functions are packaged within α-granules is controversial. One possibility is the packaging of functional agonists and antagonists into different α-granule populations. By quantitative immunofluorescence colocalization, we found that pair-wise comparisons of 15 angiogenic-relevant α-granule proteins displayed little, if any, pattern of functional coclustering. Rather, the data suggested a Gaussian distribution indicative of stochastic protein delivery to individual granules. The apparent physiologic paradox raised by these data may be explained through alternate mechanisms, such as differential content release through incomplete granule fusion or dampened and balanced regulatory networks brought about by the corelease of antagonistic factors.
authors.affiliation: Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Kamykowski
authors.forename: Peter
authors.initials: P
authors.lastname: Carlton
authors.forename: Siddharth
authors.initials: S
authors.lastname: Sehgal
authors.forename: Brian
authors.initials: B
authors.lastname: Storrie
mesh_terms: D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure; D023201:CD40 Ligand / Q000378:metabolism; D016000:Cluster Analysis; D005455:Fluorescent Antibody Technique; D006801:Humans; D016011:Normal Distribution; D019007:P-Selectin / Q000378:metabolism; D011506:Proteins / Q000378:metabolism* / Q000502:physiology; D050683:R-SNARE Proteins / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D019007:P-Selectin; D011506:Proteins; D050683:R-SNARE Proteins; C112938:VAMP8 protein, human; D023201:CD40 Ligand