Universität zu Köln

Semeniak, Daniela, Kulawig, Rebecca, Stegner, David ORCID: 0000-0003-1059-9865, Meyer, Imke, Schwiebert, Silke, Boesing, Hendrik, Eckes, Beate, Nieswandt, Bernhard and Schulze, Harald ORCID: 0000-0003-1285-6407 (2016). Proplatelet formation is selectively inhibited by collagen type I through Syk-independent GPVI signaling. J. Cell Sci., 129 (18). S. 3473 - 3485. CAMBRIDGE: COMPANY OF BIOLOGISTS LTD. ISSN 1477-9137

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Abstract

Collagen receptors GPVI (also known as GP6) and integrin alpha 2 beta 1 are highly expressed on blood platelets and megakaryocytes, their immediate precursors. After vessel injury, subendothelial collagen becomes exposed and induces platelet activation to prevent blood loss. Collagen types I and IV are thought to have opposite effects on platelet biogenesis, directing proplatelet formation (PPF) towards the blood vessels to prevent premature release within the marrow cavity. We used megakaryocytes lacking collagen receptors or treated megakaryocytes with blocking antibodies, and could demonstrate that collagen-I-mediated inhibition of PPF is specifically controlled by GPVI. Other collagen types competed for binding and diminished the inhibitory signal, which was entirely dependent on receptor-proximal Src family kinases, whereas Syk and LAT were dispensable. Adhesion assays indicate that megakaryocyte binding to collagens is mediated by alpha 2 beta 1, and that collagen IV at the vascular niche might displace collagen I from megakaryocytes and thus contribute to prevention of premature platelet release into the marrow cavity and thereby directionally promote PPF at the vasculature.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Semeniak, Daniela UNSPECIFIED UNSPECIFIED UNSPECIFIED Kulawig, Rebecca UNSPECIFIED UNSPECIFIED UNSPECIFIED Stegner, David UNSPECIFIED orcid.org/0000-0003-1059-9865 UNSPECIFIED Meyer, Imke UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwiebert, Silke UNSPECIFIED UNSPECIFIED UNSPECIFIED Boesing, Hendrik UNSPECIFIED UNSPECIFIED UNSPECIFIED Eckes, Beate UNSPECIFIED UNSPECIFIED UNSPECIFIED Nieswandt, Bernhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Schulze, Harald UNSPECIFIED orcid.org/0000-0003-1285-6407 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-262272
DOI:	10.1242/jcs.187971
Journal or Publication Title:	J. Cell Sci.
Volume:	129
Number:	18
Page Range:	S. 3473 - 3485
Date:	2016
Publisher:	COMPANY OF BIOLOGISTS LTD
Place of Publication:	CAMBRIDGE
ISSN:	1477-9137
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BONE-MARROW; GLYCOPROTEIN VI; HUMAN MEGAKARYOCYTES; PLATELET ACTIVATION; DOWN-REGULATION; RECEPTOR GPVI; INTEGRIN; EXPRESSION; MICE; THROMBOPOIESIS Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26227