A prototypic platelet septin and its participation in secretion.
Proceedings of the National Academy of Sciences. 2002-03-05; 99(5): 3064-3069
DOI: 10.1073/pnas.052715199
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1. Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3064-9.
A prototypic platelet septin and its participation in secretion.
Dent J(1), Kato K, Peng XR, Martinez C, Cattaneo M, Poujol C, Nurden P, Nurden A,
Trimble WS, Ware J.
Author information:
(1)Division of Experimental Hemostasis and Thrombosis, Department of Molecular
and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037,
USA.
Studies are presented characterizing platelet CDCrel-1, a protein expressed to
high levels by megakaryocytes and belonging to a family of conserved proteins,
termed septin. Septin filaments originally were identified in yeast as essential
for budding but have become increasingly associated with processes in higher
eukaryotic cells involving active membrane movement such as cytokinesis and
vesicle trafficking. Direct proof of an in vivo function for septins in higher
eukaryotes is limited to the characterization of the Drosophila septin, termed
PNUT. We present studies identifying platelet CDCrel-1 as a protein kinase
substrate in the presence of known platelet agonists. The immunopurification of
CDCrel-1 revealed it to be part of a macromolecular complex containing a protein
involved in platelet secretion, syntaxin 4. Moreover, CDCrel-1 was localized in
situ to areas surrounding platelet-storage granules. The relevance of CDCrel-1 to
normal platelet function was established with the characterization of platelets
from a CDCrel-1(Null) mouse. As compared with platelets from wild-type
littermates, CDCrel-1(Null) platelets aggregate and release stored [14C]serotonin
in the presence of subthreshold levels of collagen. These results provide new
insights into the mechanisms regulating platelet secretion and identify platelet
septins as a protein family contributing to membrane trafficking within the
megakaryocyte and platelet.
DOI: 10.1073/pnas.052715199
PMCID: PMC122473
PMID: 11880646 [Indexed for MEDLINE]