|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 93 No. 8 (April 15), 1999:
pp. 2617-2626
Human Platelets Contain SNARE Proteins and a Sec1p Homologue That
Interacts With Syntaxin 4 and Is Phosphorylated After Thrombin
Activation: Implications for Platelet Secretion
Guy L. Reed,
Aiilyan K. Houng, and
Michael L. Fitzgerald
From the Cardiovascular Biology Laboratory, Harvard School of Public
Health, and the Cardiac Unit, Massachusetts General Hospital, Boston,
MA.
In response to thrombin and other extracellular activators,
platelets secrete molecules from large intracellular vesicles (granules) to initiate thrombosis. Little is known about the molecular machinery responsible for vesicle docking and secretion in platelets and the linkage of that machinery to cell activation. We found that
platelet membranes contain a full complement of interacting proteins VAMP, SNAP-25, and syntaxin 4that are necessary for vesicle
docking and fusion with the plasma membrane. Platelets also contain an
uncharacterized homologue of the Sec1p family that appears to regulate
vesicle docking through its binding with a cognate syntaxin. This
platelet Sec1 protein (PSP) bound to syntaxin 4 and thereby
excluded the binding of SNAP-25 with syntaxin 4, an interaction
critical to vesicle docking. As predicted by its sequence, PSP was
detected predominantly in the platelet cytosol and was phosphorylated
in vitro by protein kinase C (PKC), a secretion-linked kinase,
incorporating 0.87 ± 0.11 mol of PO4 per mole of protein. PSP was also specifically phosphorylated in permeabilized platelets after cellular stimulation by phorbol esters or thrombin and this phosphorylation was blocked by the PKC inhibitor Ro-31-8220.
Phosphorylation by PKC in vitro inhibited PSP from binding to syntaxin
4. Taken together, these studies indicate that platelets, like neurons and other cells capable of regulated secretion, contain a unique complement of interacting vesicle docking proteins and PSP, a putative
regulator of vesicle docking. The PKC-dependent phosphorylation of PSP
in activated platelets and its inhibitory effects on syntaxin 4 binding
provide a novel functional link that may be important in coupling the
processes of cell activation, intracellular signaling, and secretion.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
L. Lian, Y. Wang, M. Flick, J. Choi, E. W. Scott, J. Degen, M. A. Lemmon, and C. S. Abrams
Loss of pleckstrin defines a novel pathway for PKC-mediated exocytosis
Blood,
April 9, 2009;
113(15):
3577 - 3584.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Procino, C. Barbieri, G. Tamma, L. De Benedictis, J. E. Pessin, M. Svelto, and G. Valenti
AQP2 exocytosis in the renal collecting duct - involvement of SNARE isoforms and the regulatory role of Munc18b
J. Cell Sci.,
June 15, 2008;
121(12):
2097 - 2106.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Flaumenhaft, N. Rozenvayn, D. Feng, and A. M. Dvorak
SNAP-23 and syntaxin-2 localize to the extracellular surface of the platelet plasma membrane
Blood,
September 1, 2007;
110(5):
1492 - 1501.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Holinstat, B. Voss, M. L. Bilodeau, and H. E. Hamm
Protease-Activated Receptors Differentially Regulate Human Platelet Activation through a Phosphatidic Acid-Dependent Pathway
Mol. Pharmacol.,
March 1, 2007;
71(3):
686 - 694.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Yacoub, J.-F. Theoret, L. Villeneuve, H. Abou-Saleh, W. Mourad, B. G. Allen, and Y. Merhi
Essential Role of Protein Kinase C{delta} in Platelet Signaling, {alpha}IIbbeta3 Activation, and Thromboxane A2 Release
J. Biol. Chem.,
October 6, 2006;
281(40):
30024 - 30035.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Oh and D. C. Thurmond
The Stimulus-induced Tyrosine Phosphorylation of Munc18c Facilitates Vesicle Exocytosis
J. Biol. Chem.,
June 30, 2006;
281(26):
17624 - 17634.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Tadokoro, M. Nakanishi, and N. Hirashima
Complexin II facilitates exocytotic release in mast cells by enhancing Ca2+ sensitivity of the fusion process
J. Cell Sci.,
May 15, 2005;
118(10):
2239 - 2246.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Martinez and J. Ware
Mammalian Septin Function in Hemostasis and Beyond
Experimental Biology and Medicine,
December 1, 2004;
229(11):
1111 - 1119.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. C. Redondo, A. G. S. Harper, G. M. Salido, J. A. Pariente, S. O. Sage, and J. A. Rosado
A role for SNAP-25 but not VAMPs in store-mediated Ca2+ entry in human platelets
J. Physiol.,
July 1, 2004;
558(1):
99 - 109.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Polgar, W. S. Lane, S.-H. Chung, A. K. Houng, and G. L. Reed
Phosphorylation of SNAP-23 in Activated Human Platelets
J. Biol. Chem.,
November 7, 2003;
278(45):
44369 - 44376.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Flaumenhaft
Molecular Basis of Platelet Granule Secretion
Arterioscler. Thromb. Vasc. Biol.,
July 1, 2003;
23(7):
1152 - 1160.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Houng, J. Polgar, and G. L. Reed
Munc18-Syntaxin Complexes and Exocytosis in Human Platelets
J. Biol. Chem.,
May 23, 2003;
278(22):
19627 - 19633.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. D. Burgoyne and A. Morgan
Secretory Granule Exocytosis
Physiol Rev,
April 1, 2003;
83(2):
581 - 632.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Rozenvayn and R. Flaumenhaft
Protein kinase C Mediates Translocation of Type II Phosphatidylinositol 5-Phosphate 4-Kinase Required for Platelet alpha -Granule Secretion
J. Biol. Chem.,
February 28, 2003;
278(10):
8126 - 8134.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Kauppi, G. Wohlfahrt, and V. M. Olkkonen
Analysis of the Munc18b-Syntaxin Binding Interface. USE OF A MUTANT Munc18b TO DISSECT THE FUNCTIONS OF SYNTAXINS 2 AND 3
J. Biol. Chem.,
November 8, 2002;
277(46):
43973 - 43979.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. W. Rutledge and S. W. Whiteheart
SNAP-23 Is a Target for Calpain Cleavage in Activated Platelets
J. Biol. Chem.,
September 27, 2002;
277(40):
37009 - 37015.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Polgar, S.-H. Chung, and G. L. Reed
Vesicle-associated membrane protein 3 (VAMP-3) and VAMP-8 are present in human platelets and are required for granule secretion
Blood,
July 18, 2002;
100(3):
1081 - 1083.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Feng, K. Crane, N. Rozenvayn, A. M. Dvorak, and R. Flaumenhaft
Subcellular distribution of 3 functional platelet SNARE proteins: human cellubrevin, SNAP-23, and syntaxin 2
Blood,
May 13, 2002;
99(11):
4006 - 4014.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Dent, K. Kato, X.-R. Peng, C. Martinez, M. Cattaneo, C. Poujol, P. Nurden, A. Nurden, W. S. Trimble, and J. Ware
A prototypic platelet septin and its participation in secretion
PNAS,
March 5, 2002;
99(5):
3064 - 3069.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Yoshioka, R. Shirakawa, H. Nishioka, A. Tabuchi, T. Higashi, H. Ozaki, A. Yamamoto, T. Kita, and H. Horiuchi
Identification of Protein Kinase Calpha as an Essential, but Not Sufficient, Cytosolic Factor for Ca2+-induced alpha - and Dense-core Granule Secretion in Platelets
J. Biol. Chem.,
October 12, 2001;
276(42):
39379 - 39385.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. L. Reed, M. L. Fitzgerald, and J. Polgar
Molecular mechanisms of platelet exocytosis: insights into the "secrete" life of thrombocytes
Blood,
November 15, 2000;
96(10):
3334 - 3342.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Chen, P. P. Lemons, T. Schraw, and S. W. Whiteheart
Molecular mechanisms of platelet exocytosis: role of SNAP-23 and syntaxin 2 and 4 in lysosome release
Blood,
September 1, 2000;
96(5):
1782 - 1788.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Riento, M. Kauppi, S. Keranen, and V. M. Olkkonen
Munc18-2, a Functional Partner of Syntaxin 3, Controls Apical Membrane Trafficking in Epithelial Cells
J. Biol. Chem.,
April 28, 2000;
275(18):
13476 - 13483.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Polgar and G. L. Reed
A Critical Role for N-ethylmaleimide-Sensitive Fusion Protein (NSF) in Platelet Granule Secretion
Blood,
August 15, 1999;
94(4):
1313 - 1318.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-H. Chung, J. Polgar, and G. L. Reed
Protein Kinase C Phosphorylation of Syntaxin 4 in Thrombin-activated Human Platelets
J. Biol. Chem.,
August 11, 2000;
275(33):
25286 - 25291.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
