Translocation of GPIb and Fc receptor gamma-chain to cytoskeleton in mucetin-activated platelets

Lu, Q; Clemetson, JM; Clemetson, KJ (2005). Translocation of GPIb and Fc receptor gamma-chain to cytoskeleton in mucetin-activated platelets. Journal of thrombosis and haemostasis, 3(9), pp. 2065-76. Oxford: Blackwell 10.1111/j.1538-7836.2005.01481.x

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Recent studies have implied that GPIb-IX-V as well as functioning as an adhesion receptor may also induce signaling to mediate binding of platelets to damaged vessel wall to prevent bleeding. Reorganization of the cytoskeleton and redistribution of platelet structural proteins and signaling molecules are thought to be important in this early activation process, though the molecular mechanisms remain to be fully defined. In this study, we have used mucetin, a snake venom lectin protein that activates platelets via GPIb, to study the redistribution of GPIb in platelets. In unstimulated platelets, a minor portion of GPIb localized to Triton-insoluble cytoskeleton fractions (TIC). This portion increased considerably after platelet activation by mucetin. We also find increased contents of the FcRgamma chain in TIC. Anti-GPIb antibodies, mocarhagin or cytochalasin D completely inhibited the cytoskeletal translocation. In addition, BAPTA-AM, a cytoplasmic calcium chelator, strongly inhibited this process. On the other hand, inhibitors of alphaIIbbeta3, PLCgamma, PKC, tyrosine kinases, ADP receptor, PI3-kinase or EDTA are effective in preventing GPIb relocation in convulxin- but not in mucetin-activated platelets. We propose that cytoskeletal translocation of GPIb is upstream of alphaIIbbeta3 activation and cross-linking of GPIb is sufficient to induce this event in mucetin-activated platelets.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Clemetson, Kenneth John

ISSN:

1538-7933

ISBN:

16102113

Publisher:

Blackwell

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:52

Last Modified:

04 May 2014 23:15

Publisher DOI:

10.1111/j.1538-7836.2005.01481.x

PubMed ID:

16102113

Web of Science ID:

000231275800025

URI:

https://boris.unibe.ch/id/eprint/22188 (FactScience: 32230)

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