Vitronectin – master controller or micromanager?

Leavesley, David I., Kashyap, Abhishek S., Croll, Tristan, Sivaramakrishnan, Manaswini, Shokoohmand, Ali, Hollier, Brett G., & Upton, Zee (2013) Vitronectin – master controller or micromanager? IUBMB Life, 65(10), pp. 807-818.

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Abstract

The concept of the cellular glycoprotein vitronectin acts as a biological ‘glue’ and key controller of mammalian tissue repair and remodelling activity is emerging from nearly 50 years of experimental in vitro and in vivo data. Unexpectedly, the vitronectin-knock-out mouse was found to be viable and to have largely normal phenotype. However, diligent observation revealed that the VN-KO animal exhibits delayed coagulation and poor wound healing. This is interpreted to indicate that vitronectin occupies a role in the earliest events of thrombogenesis and tissue repair. That role is as a foundation upon which the thrombus grows in an organised structure. In addition to closing the wound, the thrombus also serves to protect the underlying tissue from oxidation, is a reservoir of mitogens and tissue repair mediators and provides a provisional scaffold for the repairing tissue. In the absence of vitronectin (e.g. VN-KO animal) this cascade is disrupted before it begins.

Our data demonstrates that a wide variety of biologically active species associate with VN. While initial studies were focused on mitogens, other classes of bioactives (e.g. glycosaminoglycans, metalloproteinases) are now also known to specifically interact with VN. Many of these interactions are long-lived, often resulting in multi-protein complexes, while others are stable for prolonged periods. Multiprotein complexes provide several advantages: prolonging molecular interaction; sustaining local concentrations, facilitating co-stimulation of cell surface receptors and thereby enhancing cellular / biological responses. We contend that these, or equivalent, multi-protein complexes mediate vitronectin functionality in vivo. It is also likely that many of the species demonstrated to associate with vitronectin in vitro, also associate with vitronectin in vivo in similar multi-protein complexes. Thus the predominant biological function of vitronectin is that of a master controller of the extracellular environment; informing, and possibly instructing cells ‘where’ to behave, ‘when’ to behave, and ‘how’ to behave (i.e. appropriately for the current circumstance).

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ID Code: 55378
Item Type: Journal Article
Refereed: Yes
Additional Information: Conflict of Interest Statement.
The Authors have purchased shares in Tissue Therapies Ltd., an enterprise spun-out from the Queensland University of Technology, Brisbane, to commercialize some of the technology described in this manuscript.---PMID: 24030926
Keywords: Vitronectin, Extracellular Matrix, Growth Factor, Multi-protein Complex, Thrombogenesis, Coagulation
DOI: 10.1002/iub.1203
ISSN: 1521-6551
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Cell Development Proliferation and Death (060103)
Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Cellular Interactions (incl. Adhesion Matrix Cell Wall) (060106)
Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Biochemistry and Cell Biology not elsewhere classified (060199)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > MEDICAL BIOCHEMISTRY AND METABOLOMICS (110100)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > IMMUNOLOGY (110700) > Transplantation Immunology (110708)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2013 International Union of Biochemistry and Molecular Biology
Copyright Statement: The definitive version is available at www3.interscience.wiley.com
Deposited On: 11 Dec 2012 00:30
Last Modified: 27 Oct 2016 07:59

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