| First Author | Peters CG | Year | 2012 |
| Journal | Blood | Volume | 120 |
| Issue | 1 | Pages | 199-206 |
| PubMed ID | 22589474 | Mgi Jnum | J:189036 |
| Mgi Id | MGI:5444087 | Doi | 10.1182/blood-2011-10-389247 |
| Citation | Peters CG, et al. (2012) Granule exocytosis is required for platelet spreading: differential sorting of alpha-granules expressing VAMP-7. Blood 120(1):199-206 |
| abstractText | There has been recent controversy as to whether platelet alpha-granules represent a single granule population or are composed of different subpopulations that serve discrete functions. To address this question, we evaluated the localization of vesicle-associated membrane proteins (VAMPs) in spread platelets to determine whether platelets actively sort a specific subpopulation of alpha-granules to the periphery during spreading. Immunofluorescence microscopy demonstrated that granules expressing VAMP-3 and VAMP-8 localized to the central granulomere of spread platelets along with the granule cargos von Willebrand factor and serotonin. In contrast, alpha-granules expressing VAMP-7 translocated to the periphery of spread platelets along with the granule cargos TIMP2 and VEFG. Time-lapse microscopy demonstrated that alpha-granules expressing VAMP-7 actively moved from the granulomere to the periphery during spreading. Platelets from a patient with gray platelet syndrome lacked alpha-granules and demonstrated only minimal spreading. Similarly, spreading was impaired in platelets obtained from Unc13d(Jinx) mice, which are deficient in Munc13-4 and have an exocytosis defect. These studies identify a new alpha-granule subtype expressing VAMP-7 that moves to the periphery during spreading, supporting the premise that alpha-granules are heterogeneous and demonstrating that granule exocytosis is required for platelet spreading. |
