Page 2103 - Hematology_ Basic Principles and Practice ( PDFDrive )

1866 Part XII Hemostasis and Thrombosis

αllb/β3

(GPlbαβIX) V
2
Plasma
membrane
Membrane
Membrane skeleton
skeleton
Filamin
Actin
skeleton

F-actin
Microtubule
bundle
Spectrin Adducin
A B
Fig. 124.9 STRUCTURE OF THE RESTING HUMAN BLOOD PLATELET AND ITS ACTIN-BASED
CYTOSKELETON. (A) Composite illustrating the major actin cytoskeletal layers of the resting platelet.
Plasma membrane: The plasma membrane of the resting cell is flat and featureless, except for periodic invagina-
tions that lead into the open canalicular system (OCS) (arrows). Membrane skeleton: The plasma membrane
of the platelet is supported by a submembranous spectrin-based skeleton. This network is composed primarily
of spectrin molecules, which are tetramers with actin binding sites at the ends. Actin filament ends dock on
spectrin to complete the network. The association between spectrin and F actin is promoted by adducin. Actin
cytoskeleton: As discussed earlier, the spectrin network is both directly and indirectly attached to the underlying
actin filaments. Filament ends interconnect spectrin molecules, whereas the filamin links run from the filament
sides to the plasma membrane receptor (GPIbαβIX) 2V. The cytoplasmic space has a dense filling of actin fila-
ments. Actin filaments from the cell center radiate outward. As the filaments approach the plasma membrane,
they turn and run in parallel with it. The actin filaments have been decorated using myosin subfragment 1
(S1), which gives them a twisted cable-like appearance in frozen samples. Myosin S1 labeling reveals the
polarity of the actin filament. “Pointed” and “barbed” ends are definable. The ends of actin filaments are
bound by the ends of spectrin molecules on the edges of the membrane network (arrowhead). A microtubule
coil composed of a single long microtubule resides just beneath the plasma membrane at the periphery of the
thin axis of the platelet (not shown) (bar = 0.5 µm). (B) Schematic showing the structural features of the
resting blood platelet cytoskeleton. Resting cells have discoid shapes. Structural elements that support this
shape are (1) a marginal microtubule coil, (2) a spectrin-based membrane skeleton, and (3) a rigid network
of cross-linked cytoplasmic actin filaments (only a small number of the actin filaments have been added to
this illustration so that they will not obscure the rest of the structures in the cell). Platelets have a specialized
membrane skeleton composed of spectrin, actin, and many associated proteins. Spectrin tetramers (200 nm
long and 5 nm wide) have actin filament-binding sites at each molecular end. The membrane skeleton is held
in compression between the plasma membrane and the cytoplasmic actin by filamin connections from the
sides of actin filaments to the cytoplasmic tails of GPIbα subunit of the membrane glycoprotein complex that
binds to von Willebrand factor (GPIbαβIX) 2V complex. Greater than 98% of the barbed ends of actin fila-
ments are capped by adducin and capZ in the resting platelet.

are juxtaposed together and are in intimate association with the platelets, tubulin is equally divided between dimer and polymer
membranes of the OCS. The release reaction of platelet granules fractions. In many cell types, αβ-tubulin subunits are in a dynamic
differs from that of other cells. Granules rarely fuse with the plasma equilibrium with microtubules such that reversible cycles of assembly-
membrane; instead they exocytose into the OCS. Platelets also disassembly of microtubules are observed. Microtubules are long,
contain lysosomes and a few mitochondria, which are easily identified hollow polymers (24 nm in diameter) that are responsible for many
under the electron microscope by their internal system of membrane types of cellular movements, such as segregation of chromosomes
cristae. during mitosis and transport of organelles across the cell. The micro-
tubule ring of the resting platelet, initially characterized in the late
1960s by White and Krivit, was described as a single microtubule
Cytoskeleton of the Resting Platelet approximately 100 µm long and is coiled 8–12 times inside the
periphery of the platelet. However, recent work suggests that the
Although both microtubule- and actin-based forces have been con- marginal band is highly dynamic and consists of multiple microtu-
sidered in the elaboration and branching of proplatelets, respectively, bules with mixed polarity that undergo constant assembly and disas-
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it is the integration of the microtubule and actin cytoskeletal elements sembly. This may accommodate the shrinkage of microtubule coil
that uniquely defines the shape of the mature platelet. One of the diameters that occurs with aging of platelets. Antagonistic microtu-
most distinguishing features of the resting platelet is its marginal bule motors appear to keep the marginal microtubule coil in its
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microtubule coil (see Fig. 124.8). αβ-Tubulin dimers assemble resting state. The primary function of the microtubule coil is to
into microtubule polymers under physiologic conditions. In resting maintain the discoid shape of the resting platelet. Disassembly of