Procoagulant potential of platelet α granules

Polasek, J.

doi:10.1080/09537100410001721315

Cited by 18 publications

(10 citation statements)

References 47 publications

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“…In this case, higher PS levels in the "caps" could be due to the release of granules with a high PS content in their membranes. 33 Nevertheless, the binding of blood coagulation factors to these membranes allows them to get into close proximity of each other, which could promote their interaction. "Caps" are not the only place of their binding; for many, there is some interaction with the "balloon" as well.…”

Section: Discussionmentioning

confidence: 99%

Coagulation factors bound to procoagulant platelets concentrate in cap structures to promote clotting

Подоплелова¹,

Sveshnikova

Kotova

et al. 2016

Blood

106

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Key Points• All blood coagulation factors predominantly bind to a small "cap"-like region on procoagulant-activated platelets.• Their concentration in this small region promotes acceleration of the membrane-dependent reactions of coagulation.Binding of coagulation factors to phosphatidylserine (PS)-exposing procoagulant-activated platelets followed by formation of the membrane-dependent enzyme complexes is critical for blood coagulation. Procoagulant platelets formed upon strong platelet stimulation, usually with thrombin plus collagen, are large "balloons" with a small (∼1 mm radius) "cap"-like convex region that is enriched with adhesive proteins. Spatial distribution of blood coagulation factors on the surface of procoagulant platelets was investigated using confocal microscopy. All of them, including factors IXa (FIXa), FXa/FX, FVa, FVIII, prothrombin, and PS-sensitive marker Annexin V were distributed nonhomogeneously: they were primarily localized in the "cap," where their mean concentration was by at least an order of magnitude, higher than on the "balloon." Assembly of intrinsic tenase on liposomes with various PS densities while keeping the PS content constant demonstrated that such enrichment can accelerate this reaction by 2 orders of magnitude. The mechanisms of such acceleration were investigated using a 3-dimensional computer simulation model of intrinsic tenase based on these data. Transmission electron microscopy and focal ion beam-scanning electron microscopy with Annexin V immunogold-labeling revealed a complex organization of the "caps." In platelet thrombi formed in whole blood on collagen under arterial shear conditions, ubiquitous "caps" with increased Annexin V, FX, and FXa binding were observed, indicating relevance of this mechanism for surface-attached platelets under physiological flow. These results reveal an essential heterogeneity in the surface distribution of major coagulation factors on the surface of procoagulant platelets and suggest its importance in promoting membrane-dependent coagulation reactions. (Blood. 2016;128(13):1745-1755

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Section: Discussionmentioning

confidence: 99%

Coagulation factors bound to procoagulant platelets concentrate in cap structures to promote clotting

Подоплелова¹,

Sveshnikova

Kotova

et al. 2016

Blood

106

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“…These granules are translocated to the surface after cell activation, transferring CD63 into the plasma membrane. This surface expression of CD63 in platelets serves as an important diagnostic activation marker (39,64).…”

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confidence: 99%

Deficiency of the Tetraspanin CD63 Associated with Kidney Pathology but Normal Lysosomal Function

Schröder

Lüllmann‐Rauch

Himmerkus

et al. 2009

Molecular and Cellular Biology

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CD63 is a member of the tetraspanin superfamily that constitutes a main component of the lysosomal membrane. In mice, two CD63 gene loci are present, with only one of these two being functional. We generated and analyzed mice deficient for active CD63. Disruption of CD63 results in a complete loss of CD63 protein expression. Despite its abundance in late endosomes/lysosomes, the lack of CD63 does not cause obvious endosomal/lysosomal abnormalities. CD63 knockout mice are viable and fertile without gross morphological abnormalities in the majority of tissues. No alterations in the populations of immune cells and only minor differences in platelet function were observed. This suggests that the lack of CD63 could be successfully compensated for, most likely by other tetraspanins. However, CD63 deficiency leads to an altered water balance. CD63 knockout mice show an increased urinary flow, water intake, reduced urine osmolality, and a higher fecal water content. In principle cells of the collecting duct of CD63-deficient mice, abnormal intracellular lamellar inclusions were observed. This indicates that the sorting of apical transport proteins might be impaired in these cells. CD63 knockout mice provide an important tool for analyzing the various postulated functions of CD63 in vivo.

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“…The fact that acid phosphatases are difficult to detect in alpha granules histochemically [1], can be explained by the lower sensitivity of histochemical methods compared to biochemical methods, obviously due to tightly packed glycoproteins in alpha granules. Subcellular fractionation of platelet secretory organelles showed that the typical lysosomal enzyme acid phosphatase can be detected practically in every fraction, which means also in the alpha granules fraction, as reviewed in [7,9]. One should bring up here the not well known fact that platelet lysosomal acid phosphatase cannot be solubilised even by detergents and exists always in a form firmly bound to lipoprotein membranes -as discussed in [7,9].…”

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confidence: 99%

“…It was shown for example that alpha granules are able to incorporate plasma fibrinogen, albumin or factor V -for references see [9]. It should be mentioned that isolated platelet alpha granules show the presence of lysosomal acid phosphatases biochemically [8] and have an acidic interior as mentioned above [5].…”

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confidence: 99%