A novel platelet protein Reln regulates platelet function through modulation of PKCdelta and small GTPase activity
碩士 === 長庚大學 === 醫學生物技術研究所 === 96 === Reelin (Reln) is an extracellular matrix protein that plays a pivotal role in neuronal cell migration and is abundantly expressed in the plasma. However, the expression and function of Reln in the hematopoietic cells are barely characterized. In this study, we fo...
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ndltd-TW-096CGU056040172016-05-13T04:15:01Z http://ndltd.ncl.edu.tw/handle/38945956555468771221 A novel platelet protein Reln regulates platelet function through modulation of PKCdelta and small GTPase activity Reln蛋白於血小板中藉由改變PKCdelta及smallGTPase活性調控血小板功能 Wei Lian Tseng 曾維廉 碩士 長庚大學 醫學生物技術研究所 96 Reelin (Reln) is an extracellular matrix protein that plays a pivotal role in neuronal cell migration and is abundantly expressed in the plasma. However, the expression and function of Reln in the hematopoietic cells are barely characterized. In this study, we found that Reln was expressed in the megakaryocyte-like leukemic cell lines and human platelets. Subcellular localization analysis revealed that Reln distributed in the platelet a-granules and was released into the supernatant upon platelet activation. The lack of Reln mRNA in the platelet indicates that Reln was not generated endogenously by platelet. Instead, plasma could be the source for platelet. Consistent with these observations, we found that extracellular Reln recombinant protein is associated with the platelet. Platelet-Reln interaction was also revealed by a platelet adhesion assay toward the Reln-coated slides. During platelet adhesion to fibrinogen, the Reln-platelet interactions result in an increase in platelet spreading, lamellipodia formation and F-actin bundling. Such effects were diminished by the presence of Reln blocking antibody CR-50, indicating that Reln is a regulator of platelet spreading. Further analysis revealed that Reln signaling inhibited PKC activation and increased Rac1 ativity. Consistent with this observation, the Rac1 inhibitor NSC23766 reversed Reln effect on platelet spreading. These findings demonstrate for the first time that Reln plays a novel role in the control of platelet-fibrinogen interactions with modulation of PKC and Rac1 activity as the underlying mechanism. C. P. Tseng 曾慶平 2008 學位論文 ; thesis 51 |
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碩士 === 長庚大學 === 醫學生物技術研究所 === 96 === Reelin (Reln) is an extracellular matrix protein that plays a pivotal role in neuronal cell migration and is abundantly expressed in the plasma. However, the expression and function of Reln in the hematopoietic cells are barely characterized. In this study, we found that Reln was expressed in the megakaryocyte-like leukemic cell lines and human platelets. Subcellular localization analysis revealed that Reln distributed in the platelet a-granules and was released into the supernatant upon platelet activation. The lack of Reln mRNA in the platelet indicates that Reln was not generated endogenously by platelet. Instead, plasma could be the source for platelet. Consistent with these observations, we found that extracellular Reln recombinant protein is associated with the platelet. Platelet-Reln interaction was also revealed by a platelet adhesion assay toward the Reln-coated slides. During platelet adhesion to fibrinogen, the Reln-platelet interactions result in an increase in platelet spreading, lamellipodia formation and F-actin bundling. Such effects were diminished by the presence of Reln blocking antibody CR-50, indicating that Reln is a regulator of platelet spreading. Further analysis revealed that Reln signaling inhibited PKC activation and increased Rac1 ativity. Consistent with this observation, the Rac1 inhibitor NSC23766 reversed Reln effect on platelet spreading. These findings demonstrate for the first time that Reln plays a novel role in the control of platelet-fibrinogen interactions with modulation of PKC and Rac1 activity as the underlying mechanism.
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author2 |
C. P. Tseng |
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C. P. Tseng Wei Lian Tseng 曾維廉 |
author |
Wei Lian Tseng 曾維廉 |
spellingShingle |
Wei Lian Tseng 曾維廉 A novel platelet protein Reln regulates platelet function through modulation of PKCdelta and small GTPase activity |
author_sort |
Wei Lian Tseng |
title |
A novel platelet protein Reln regulates platelet function through modulation of PKCdelta and small GTPase activity |
title_short |
A novel platelet protein Reln regulates platelet function through modulation of PKCdelta and small GTPase activity |
title_full |
A novel platelet protein Reln regulates platelet function through modulation of PKCdelta and small GTPase activity |
title_fullStr |
A novel platelet protein Reln regulates platelet function through modulation of PKCdelta and small GTPase activity |
title_full_unstemmed |
A novel platelet protein Reln regulates platelet function through modulation of PKCdelta and small GTPase activity |
title_sort |
novel platelet protein reln regulates platelet function through modulation of pkcdelta and small gtpase activity |
publishDate |
2008 |
url |
http://ndltd.ncl.edu.tw/handle/38945956555468771221 |
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