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PubMed1996

Skeletonized and pedicled internal thoracic artery grafts: effect on free flow during bypass.

BACKGROUND: The skeletonization technique of the internal thoracic artery (ITA) is used as a dissection technique for myocardial revascularization procedures. This study compared free flow between skeletonized ITA grafts and ITA pedicled grafts. METHODS: The ITA pedicled grafts were sprayed and wrapped in sponges soaked in dilute papaverine solution in 14 patients and prepared with intraluminal papaverine injection in 18 patients. For 23 other patients, the ITA was skeletonized. We measured the first free flow from the distal ITA early after the start of cardiopulmonary bypass and the second free flow just before the ITA was grafted to the left anterior descending artery. RESULTS: The first flow was greater in the skeletonized ITAs than in the ITA pedicled grafts with topical application of papaverine alone (38.9 +/- 15.8 versus 18.0 +/- 6.8 mL/min; p < 0.001). For the second flow, the pedicle grafts with intraluminal papaverine injection and the skeletonized ITAs showed greater flow rate than the pedicled grafts with topical application of papaverine (67.4 +/- 25.5 and 59.7 +/- 22.5 versus 38.1 +/- 13.1 mL/min; p < 0.005 and p < 0.05, respectively), but there was no significant difference between the former two groups (p = 0.53). CONCLUSIONS: Skeletonization of the ITA is as efficient a strategy to increase the flow as intraluminal papaverine injection for the ITA pedicled graft. When the ITA is harvested in a skeletonized fashion, arterial spasm and reduced early flow can be avoided, even without intraluminal injection of papaverine.

Adult↗

PubMed1994

The interaction of N-formyl peptide chemoattractant receptors with the membrane skeleton is energy-dependent.

Desensitization of N-formyl peptide chemoattractant receptors (FPR) in human neutrophils is thought to be achieved by lateral segregation of receptors and G proteins within the plane of the plasma membrane resulting in an interruption of the signalling cascade. Direct coupling of FPR to membrane skeletal actin appears to be the basis of this process; however, the molecular mechanism is unknown. In this study we investigated the effect of energy depletion on formation of FPR-membrane skeleton complexes. In addition the effect of the protein kinase C inhibitor stauroporine and the phosphatase inhibitor okadaic acid on coupling of FPR to the membrane skeleton was studied. Human neutrophils were desensitized using the photoreactive agonist N-formyl-met-leu-phe-lys-N'-[125I]2(p-azidosalicylamido)ethyl-1,3' - dithiopropionate (fMLFK-[125I]ASD) after ATP depletion with NaF or after incubation with the respective inhibitors. The interaction of FPR with the membrane skeleton was studied by sedimentation of the membrane skeleton-associated receptors in sucrose density gradients. Energy depletion of the cells markedly inhibited the formation of FPR-membrane skeleton complexes. This does not appear to be related to inhibition of protein phosphorylation due to ATP depletion because inhibition of protein kinases and phosphatases had no significant effect on coupling of FPR to the membrane skeleton. We conclude, therefore, that coupling of FPR to the membrane skeleton is an energy-dependent process which does not appear to require modification of the receptor protein by phosphorylation.

Alkaloids↗

PubMed2004

Robotic skeletonizing of the internal thoracic artery: is it safe?

BACKGROUND: The advantages of internal thoracic artery skeletonization include early high blood flow, a longer conduit, and less bleeding than pedicle internal thoracic artery grafts. Longer conduits are needed for complete endoscopic arterial revascularization. Therefore this study was designed to determine the feasibility and safety of internal thoracic artery skeletonization using the da Vinci robotic system (Intuitive Surgical, Sunnyvale, CA). METHODS: Nine dogs underwent bilateral robotic internal thoracic artery harvesting through three ports placed in the left chest. One internal thoracic artery was harvested as a pedicle in each dog, and the other was skeletonized. Internal thoracic artery blood flow was measured in each graft, and comparative endothelial histologic studies were performed. Data are mean +/- the standard error of the mean. RESULTS: All 18 internal thoracic arteries were harvested successfully. Skeletonized internal thoracic artery harvests required more time (48.0 minutes +/- 1.8) than pedicle internal thoracic artery harvests (39.0 minutes +/- 1.4; p < 0.05). Internal thoracic artery flows during the final intervals were similar (skeletonized = 30.0 mL/min +/- 2.4 vs pedicle = 31.5 mL/min +/- 1.8; p = 0.9). Free internal thoracic artery bleeding flow was similar in both groups (skeletonized = 162.0 mL/min +/- 3.0 vs pedicle = 189.0 mL/min +/- 2.4; p = 0.4). Histologically, both groups were similar with minimal endothelial damage. CONCLUSIONS: Robotically skeletonized harvesting is safe, but it requires more time (48.0 minutes +/- 1.8) than pedicle internal thoracic artery harvesting. Despite muted tactile feedback with robotics, neither technique was associated with histologic or functional damage. These encouraging results may represent an advantage for complete arterial revascularization in robotic coronary bypass patients.

Animals↗

PubMed2005

The two-step mode of growth in the scleractinian coral skeletons from the micrometre to the overall scale.

It has been known since the 19th century that coral skeletons are built of aragonite crystals with taxonomy-linked arrangements, but the way by which each coral species controls this crystallization process remains an unsolved question. The problem became still more intriguing when it was shown that isotopic compositions of coral aragonite were subject to taxonomy-linked influences (the "vital effect"). On the other hand, presence of an organic component in coral skeletons is also long known, but localization of these compounds is admittedly restricted to particular structures called "centres of calcifications." Fibres, the largely predominant part of the coral skeletons, are usually considered as purely mineral units. In this paper, it is shown that in both "centres of calcification" and fibres, organic compounds are associated with the mineral material at a deep structural level. A series of variously scaled observations and localized measurements allow recognition of the presence of an organic component at the nanometre scale. Far from being a freely operating process, crystallization of coral fibres is thus permanently controlled by the polyp basal ectoderm through a cyclic two-step process acting at the micrometre-scale. The biomineralization cycle begins by secretion of a proteoglycan matrix. As the composition of these sugars-proteins assemblages has been shown taxonomy dependent, the hypothesis can be made that multiple and long recognized specificities of coral skeletons are linked to this biochemically driven crystallization process. Additionally, this new concept of the biomineralization process in coral skeletons provides us with an access to the long term evolution of the Scleractinia. Remarkably, results of a skeleton-based approach using microstructural criteria (i.e., the spatial relationships of "centres of calcification" and the three-dimensional arrangements of fibres), are consistent with a molecular phylogenetic analysis carried out on the same species. Clearly, at the overall ontogenic level, the two-step growth mode of coral skeletons is also a valuable tool to reconstruct the evolutionary history of Scleractinia.

Acridine Orange↗

PubMed1999

Free flow capacity of skeletonized versus pedicled internal thoracic artery grafts in coronary artery bypass grafts.

OBJECTIVE: The internal thoracic artery (ITA) is the ideal conduit for coronary artery bypass grafting (CABG). The skeletonization technique of this arterial conduit has been proposed to reduce chest wall trauma, increase graft length and facilitate construction of sequential anastomoses. Nevertheless, some surgeons decline this technique because of potentially increased trauma to the ITA with impairment of flow. In this investigation we compared the free flow of skeletonized with that of pedicled ITA grafts. METHODS: Two surgeons operated on 80 consecutive patients with coronary artery disease for elective CABG. In group I (n = 40), the left ITA was dissected using the skeletonization technique. In group II (n = 40), it was harvested as a pedicled graft. In 23 patients of group I both ITA's were dissected in skeletonized fashion for complete arterial revascularization. Diluted papaverine was instilled into the lumen of the ITA after distal transection of the vessel in both groups. Free flow of the ITA was registered before and 15 min after intraluminal application of diluted papaverine. Mean arterial pressure was maintained at 70 mmHg. RESULTS: Before the application of papaverine, free flow of skeletonized and pedicled ITA grafts was identical between the two groups. After treatment with papaverine maximum free flow was significantly higher in the skeletonized ITA's (group I 197.2 (+/-66.6) ml/min; group II 147.1 (+/-70.5) ml/min; P < 0.05). There was no significant difference between free flow after dilatation of the left and right ITA in group I (left 197.2 (+/-66.6) ml/min; right 198.9 (+/-61.8) ml/min). CONCLUSIONS: Preparation of the ITA with the skeletonization technique results in significantly, higher free flow capacity than in pedicled grafts. This may increase the safety of arterial revascularization by reducing the risk of ITA hypoperfusion syndrome.

Aged↗

PubMed2006

Spatially variant morphological restoration and skeleton representation.

The theory of spatially variant (SV) mathematical morphology is used to extend and analyze two important image processing applications: morphological image restoration and skeleton representation of binary images. For morphological image restoration, we propose the SV alternating sequential filters and SV median filters. We establish the relation of SV median filters to the basic SV morphological operators (i.e., SV erosions and SV dilations). For skeleton representation, we present a general framework for the SV morphological skeleton representation of binary images. We study the properties of the SV morphological skeleton representation and derive conditions for its invertibility. We also develop an algorithm for the implementation of the SV morphological skeleton representation of binary images. The latter algorithm is based on the optimal construction of the SV structuring element mapping designed to minimize the cardinality of the SV morphological skeleton representation. Experimental results show the dramatic improvement in the performance of the SV morphological restoration and SV morphological skeleton representation algorithms in comparison to their translation-invariant counterparts.

Algorithms↗

PubMed1999

Dynamic rearrangement of the spectrin membrane skeleton during the generation of epithelial polarity in Drosophila.

The origin of epithelial cell polarity during development is a fundamental problem in cell biology. Central to this process is the establishment of asymmetric membrane domains that will ultimately form the apical and basolateral surfaces. The spectrin-based membrane skeleton has long been thought to participate in the generation of this asymmetry. Drosophila melanogaster contains two known (beta)-spectrin isoforms: a conventional (beta)-spectrin chain, and the novel isoform (beta)(Heavy)-spectrin. These two proteins are restricted to the basolateral and apical membrane domains, respectively. To assay for the emergence of membrane asymmetry, we have characterized the distribution of these two (beta)-spectrins during the formation of the primary epithelium in the fly embryo. Our results show that the syncytial embryo contains a maternally established apical membrane skeleton containing (beta)(Heavy)-spectrin into which the basolateral (beta)-spectrin membrane skeleton is added. We have called this process basolateral interpolation. Although basolateral membrane skeleton addition begins during cellularization, it does not become fully established until the formation of a mature zonula adherens at mid to late gastrulation. The behavior of (beta)-spectrin is consistent with a primary role in establishing and/or maintaining the basolateral domain while the behavior of (beta)(Heavy)-spectrin suggests that its primary role is associated with a specialized DE-cadherin complex associated with the furrow canals and with the maturation of the zonula adherens. Thus, the apical spectrin membrane skeleton appears to play a distinct rather than analogous role to the basolateral spectrin membrane skeleton, during the emergence of cell polarity. We find that there are several parallels between our observations and previous studies on the establishment of primary epithelial polarity in vertebrates, suggesting that basolateral interpolation of the membrane skeleton may be a common mechanism in many organisms.

Animals↗

PubMed1994

Midline maxillofacial skeleton in human anencephalic fetuses.

The purpose of this study was to describe the midline maxillofacial skeleton (the axial skeleton anterior to the sella turcica) in 15 human anencephalic fetuses (14-19 weeks of gestation) by radiography and histology, and to relate the findings to skeletal patterns in the remaining part of the axial skeleton. Four patterns in the maxillofacial skeleton were recognized: normal structures, slightly deformed (6 cases); cleft palate (3 cases); incomplete nasal septum (3 cases); multilocular ethmoid cartilage (3 cases). No association was found between skeletal patterns in the different parts of the axial skeleton. The study demonstrates the existence of a developmental borderline in the anencephalic axial skeleton in the region of the sella turcica. It is presumed that this borderline indicates the boundary between skeletal tissue developed around the notochord (posterior axial skeleton) and the anterior skeletal components derived from neural crest cells.

Anencephaly↗

PubMed2005

Using an approximation to the euclidean skeleton for efficient collision detection and tissue deformations in surgical simulators.

This paper describes a technique for efficient collision detection and deformation of abdominal organs in surgical simulation using an approximation of the Euclidean skeleton. Many researchers have developed surgical simulators, but one of the most difficult underlying problems is that of organ-instrument collision detection followed by the deformation of the tissue caused by the instrument. Much of the difficulty is due to the vast number of polygons in high resolution complex organ models. A high resolution gall bladder model for instance can number in the tens of thousands of polygons. Our methodology utilizes the reduction power of the skeleton to reduce computations. First, we recursively compute approximations to the Euclidean skeleton to generate a set of skeletal points for the organ. Then we pre-compute for each vertex in each polygon the associated skeleton point (minimal distance discs). A spring is then connected from each vertex to its associated skeleton point to be used in the deformation algorithm. The data structure for the organ thus stores for each skeletal point its maximum and minimum distances and the list of associated vertices. A heuristic algorithm using the skeleton structure of the instrument and the skeleton of the organ is used to determine instrument collisions with the organ.

Computer Simulation↗

PubMed2000

Involvement of an F-actin skeleton on the acrosome reaction in guinea pig spermatozoa.

The acrosome reaction (AR) is a regulated exocytotic process. In several cell types, an actin network situated under the plasma membrane (PM) acts as a physical barrier to prevent this exocytosis. In seeking a function for a cortical skeleton in guinea pig spermatozoa, the PM and the outer acrosomal membrane (OAM) were investigated for the presence of F-actin and spectrin, proteins generally found in cell cortical skeletons. Both membrane types were visualized in whole-mount preparations by electron microscopy. PM proteins gave positive reaction to the Na(+),K(+)-ATPase antibody and the OAM proteins did not react to the antibody. Furthermore, a Triton X-100-resistant skeleton was obtained from both membrane types. Using gold immunoelectron microscopy, F-actin was visualized in the PM and in the OAM skeletons, while spectrin was only detected in the PM skeleton. The presence of an F-actin cortical skeleton in the sperm PM suggests that F-actin may be involved in the AR. The significantly higher number of AR elicited by cytochalasin D (Cyt-D) treatment(P<0.005) and data showing a significant (P>0.03) decrease in F-actin relative concentration in capacitating spermatozoa, agree with this suggestion. Furthermore, the proposal is strengthened by the fact that stabilization of F-actin by phalloidin (Ph) significantly (P>0.01) diminished AR induced by Ca(2+) in a streptolysin O (SLO)-permeabilized sperm model.

Acrosome Reaction↗

PubMed1999

Effects of Ca2+ on erythrocyte membrane skeleton-bound phosphofructokinase, ATP levels, and hemolysis.

Erythrocyte Ca2+ overload is known to occur in several different disease states, and to affect the erythrocyte membrane deformability. We show here that an increase in intracellular Ca2+ concentration in erythrocytes, induced by ionomycin, caused a reduction in ATP levels. Concomitant to the fall in ATP, a marked activation of phosphofructokinase (PFK) (EC 2.7.1.11), the rate-limiting enzyme in glycolysis, in the membrane skeleton fraction occurred. The increase in the membrane skeleton-bound PFK activity was most probably mediated by Ca2+, as direct addition of Ca2+ to the membrane skeleton fraction from the erythrocyte induced an enhancement of the bound PFK activity. Time-response curves revealed that erythrocyte hemolysis did not occur during the first 30 min of incubation with ionomycin, when the membrane skeleton-bound PFK was activated. Longer incubation time resulted in solubilization of the membrane skeleton-bound PFK and a concomitant hemolysis of the erythrocytes. These results suggest that the Ca2+-induced activation of membrane skeleton-bound PFK, and thereby glycolysis, the sole source of energy in erythrocytes, may be a defense mechanism to surmount the damage induced by high Ca2+ levels.

Adenosine Triphosphate↗

PubMed2004

Role of the membrane skeleton in creation of microdomains.

The membrane skeleton is a specialized part of the cytoskeleton that is in close proximity to the cell membrane with a protein composition and structure that differs from that of the bulk cytoskeleton. The membrane skeleton and various transmembrane proteins bound to it form a mosaic of compartments in the membrane that is responsible for the temporary confinement of membrane proteins and lipids and controls the rate of their repetitive hop movements between these membrane skeleton-based compartments, known as "hop diffusion", found by observation of single-molecule diffusion. Such hop diffusion has been found to be universal with compartment sizes that range from 30 to 700 nm, depending on the cell type. The part of the membrane skeleton that is directly involved in temporal confinement of membrane molecules has been successfully imaged by raster scanning a single membrane molecule using an optical trap (single molecule scanning optical force imaging). Such compartmentalization enables dynamic spatial regulation of signal transduction in the plasma membrane, by arresting signaling complexes of activated receptor molecules and enlarged, stabilized rafts within a compartment. Furthermore, high concentrations of the membrane skeleton and its associated immobile transmembrane proteins are involved in formation of the cell membrane polarity such as is found across the initial segment between the axon and the cell body in neurons. Argument is advanced that the creation of various membrane domains in the cell membrane must be influenced by the membrane skeleton.

Animals↗

PubMed1981

Analysis of entrainment of circadian oscillators by skeleton photoperiods using phase transition curves.

A skeleton photoperiod consists of two short pulses which are applied on the circadian oscillator at times corresponding to the beginning and to the end of a continuous light stimulus. To study several problems in entrainment of circadian rhythms by skeleton photoperiods, we develop a simple diagrammatic solution of the steady state entrainment making use of phase transition curves which are directly gotten from phase response curves. The graphical method is simple and systematic to study entrainment by light cycles with various day lengths. As the method is also intuitive, we can easily examine three problems. (1) In Drosophila the phase relation (psi) between rhythm and light cycle is a continuous function of day length of skeleton photoperiods up to about 12 h, but a marked discontinuity (psi-jump) sets in between 13 and 14 h. By the diagrammatic method we find that psi-jump is mathematically a bifurcation phenomenon. (2) The action of photoperiods up to about 12 h is fully simulated by two 15-min skeleton pulses. Do 3-min skeleton pulses imitate the complete photoperiods? We find that pulse width is arbitrary to some extent. (3) Why skeleton photoperiods up to about 12 h are good models of complete photoperiods? The reason is the small amplitude and the nearly symmetrical form of phase response curves in the subjective day.

Animals↗

PubMed2003

Does skeletonization compromise the integrity of internal thoracic artery grafts?

BACKGROUND: There are few reports that demonstrate the chronologic changes in the functional integrity of the internal thoracic artery (ITA) wall after skeletonization. We investigated the impact of skeletonization on ITA wall integrity by immunohistochemical analyses in acute and chronic phases. METHODS: Nine mongrel dogs underwent bilateral ITA dissection with one skeletonized vessel and the other pedicled. The following studies were performed 1 week (acute phase, n = 3) and 12 weeks (chronic phase, n = 6) after ITA harvesting. All specimens of the ITAs were stained by antibodies against von Willebrand Factor (VWF), endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and proliferating cell nuclear antigen (PCNA). After observation with confocal laser scanning microscopy, quantitative analyses of the staining signal for VWF and eNOS expressed on endothelial cells were performed. RESULTS: There were significantly more microvessels positive for VWF in the adventitia of skeletonized ITAs than in the adventitia of pedicled ITAs but the expression of PCNA in both groups was minimal, as in normal vessels. iNOS was not detected in any specimen. The intensity of VWF and eNOS expressed by endothelial cells had no significant differences between groups at either phase. CONCLUSIONS: The functional integrity of skeletonized ITA was similar to that of pedicled ITA in both acute and chronic phases. Although skeletonization induced neovascularization in the adventitia it did not induce proliferation of smooth muscle cells in the media, which is supposed to be a feature of vascular remodeling.

Animals↗

PubMed1998

Effect of skeletonizing dissection on the internal thoracic artery.

BACKGROUND: Skeletonization of the internal thoracic artery (ITA) produces greater length for coronary bypass grafting. We studied the effect of skeletonization on the morphology, histology, and tissue viability of the ITA wall. METHODS: Six mongrel dogs underwent unilateral ITA dissection; the contralateral ITA was the control. Study periods were 3 weeks (n=3) and 12 weeks (n=3). At sacrifice, the entire anterior chest wall was removed and dynamically fixed with formalin. Extensive histologic comparisons were performed on three tissue blocks taken from each ITA, 2, 8, and 24 cm from their origin. RESULTS: Flows at the end of the study were comparable to measurements taken during operation, immediately after skeletonization. Grossly, the ITA wall was not injured by skeletonization and there was no adventitial hematoma or bleeding from the sealed branch ends. Microscopic observations showed intact, normal wall structures. Histologic data showed no major significant difference between controls and skeletonized ITAs. CONCLUSIONS: Careful skeletonizing dissection is not detrimental to the integrity of ITAs, which justifies their use for myocardial revascularization.

Animals↗

PubMed2000

The spectrin skeleton of newly-invaginated plasma membrane.

As a cell's shape and volume change. its surface area must re-adjust. How is the plasma membrane's spectrin skeleton implicated? For erythrocytes, cells of fixed surface area, spectrin responses to mechanical disturbances have been studied, but for more typical cells with changeable surface areas, they have not. In rapidly shrinking cells, surface membrane at an adherent substratum invaginates, forming transient vacuole-like dilations (VLDs). We exploited this readily inducible surface area perturbation to pose a simple question: is newly invaginated plasma membrane naked or is it supported by a spectrin skeleton? The spectrin skeleton was examined immunocytochemically in L6 cells (rat skeletal muscle) before and after VLD formation, using fixation in cold methanol and 4112, an antibody against beta-fodrin and beta-spectrin. 4112 was visualized by confocal fluorescence microscopy, while paired phase contrast images independently located the VLDs. To generate VLDs, cells were hypotonically swelled then reshrunk in isotonic medium. Swollen L6 cells maintained their plasma membrane (sarcolemma) spectrin skeleton. Within minutes of subsequent shrinkage, VLDs of 1-2 microm diameter invaginated at the substratum surface of myotubes. Both sarcolemma and VLDs were lined by a relatively uniform spectrin skeleton. Z-series suggested that some of the spectrin skeleton-lined sarcolemma became internalized as vacuoles.

Animals↗

PubMed2001

Atomic force microscopy of the erythrocyte membrane skeleton.

The atomic force microscope was used to examine the cytoplasmic surface of untreated as well as fixed human erythrocyte membranes that had been continuously maintained under aqueous solutions. To assess the effects of drying, some membranes were examined in air. Erythrocytes attached to mica or glass were sheared open with a stream of isotonic buffer, which allowed access to the cytoplasmic membrane face without exposing cells to non-physiological ionic strength solutions. Under these conditions of examination, the unfixed cytoplasmic membrane face revealed an irregular meshwork that appeared to be a mixture largely of triangular and rectilinear openings with mesh sizes that varied from 35 to 100 nm, although few were at the upper limit. Fixed ghosts were similar, but slightly more contracted. These features represent the membrane skeleton, as when the ghosts were treated to extract spectrin and actin, these meshworks were largely removed. Direct measurements of the thickness of the membrane skeleton and of the lateral dimensions of features in the images suggested that, especially when air dried, spectrin can cluster into large, quite regularly distributed aggregates. Aggregation of cytoskeletal components was also favoured when the cells were attached to a polylysine-treated substrate. In contrast, the membrane skeletons of cells attached to substrates rendered positively charged by chemical derivatization with a cationic silane were much more resistant to aggregation. As steps were taken to reduce the possibility of change of the skeleton after opening the cells, the aggregates and voids were eliminated, and the observed structures became shorter and thinner. Ghosts treated with Triton X-100 solutions to remove the bilayer revealed a meshwork having aggregated components resembling those seen in air. These findings support the proposition that the end-to-end distance of spectrin tetramers in the cell in the equilibrium state is much shorter than the contour length of the molecule and that substantial rearrangements of the spectrin-actin network occur when it is expanded by low ionic strength extraction from the cell. This study demonstrates the applicability of AFM for imaging the erythrocyte membrane skeleton at a resolution that appears adequate to identify major components of the membrane skeleton under near-physiological conditions.

Actins↗

PubMed1995

Dystrophin-related protein in the platelet membrane skeleton. Integrin-induced change in detergent-insolubility and cleavage by calpain in aggregating platelets.

The platelet membrane is lined with a membrane skeleton that associates with transmembrane adhesion receptors and is thought to play a role in regulating the stability of the membrane, distribution and function of adhesive receptors, and adhesive receptor-induced transmembrane signaling. When platelets are lysed with Triton X-100, cytoplasmic actin filaments can be sedimented by centrifugation at low g-forces (15,600 x g) but the membrane skeleton requires 100,000 x g. The present study shows that DRP (dystrophin-related protein) sediments from lysed platelets along with membrane skeleton proteins. Sedimentation results from association with the membrane skeleton because DRP was released into the detergent-soluble fraction when actin filaments were depolymerized. Interaction of fibrinogen with the integrin alpha IIb beta 3 induces platelet aggregation, transmembrane signaling, and the formation of integrin-rich cytoskeletal complexes that can be sedimented from detergent lysates at low g-forces. Like other membrane skeleton proteins, DRP redistributed from the high-speed pellet to the integrin-rich low-speed pellet of aggregating platelets. One of the signaling enzymes that is activated following alpha IIb beta 3-ligand interactions in a platelet aggregate is calpain; DRP was cleaved by calpain to generate an approximately 140-kDa fragment that remained associated with the low-speed detergent-insoluble fraction. These studies show that DRP is part of the platelet membrane skeleton and indicate that DRP participates in the cytoskeletal reorganizations resulting from signal transmission between extracellular adhesive ligand and the interior of the cell.

Amino Acid Sequence↗