Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/36688
Title: Intermolecular interactions of thrombospondins drive their accumulation in extracellular matrix
Authors: Kim, D. J.
Christofidou, Elena D.
Keene, D. R.
Milde, M. H.
Adams, J. C.
First Published: 20-May-2015
Publisher: American Society for Cell Biology
Citation: Molecular Biology of the Cell July 15, 2015 vol. 26 no. 14 2640-2654
Abstract: Thrombospondins participate in many aspects of tissue organization in adult tissue homeostasis, and their dysregulation contributes to pathological processes such as fibrosis and tumor progression. The incorporation of thrombospondins into extracellular matrix (ECM) as discrete puncta has been documented in various tissue and cell biological contexts, yet the underlying mechanisms remain poorly understood. We find that collagen fibrils are disorganized in multiple tissues of Thbs1−/− mice. In investigating how thrombospondins become retained within ECM and thereby affect ECM organization, we find that accumulation of thrombospondin-1 or thrombospondin-5 puncta within cell-derived ECM is controlled by a novel, conserved, surface-exposed site on the thrombospondin L-type lectin domain. This site acts to recruit thrombospondin molecules into ECM by intermolecular interactions in trans. This mechanism is fibronectin independent, can take place extracellularly, and is demonstrated to be direct in vitro. The trans intermolecular interactions can also be heterotypic—for example, between thrombospondin-1 and thrombospondin-5. These data identify a novel concept of concentration-dependent, intermolecular “matrix trapping” as a conserved mechanism that controls the accumulation and thereby the functionality of thrombospondins in ECM.
DOI Link: 10.1091/mbc.E14-05-0996
ISSN: 1059-1524
eISSN: 1939-4586
Links: http://www.molbiolcell.org/content/26/14/2640
http://hdl.handle.net/2381/36688
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: © 2015 Kim, Christofidou, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by -nc-sa/3.0).
Description: Supplemental Material can be found at: http://www.molbiolcell.org/content/suppl/2015/05/18/mbc.E14-05-0996v1.DC1.html
Appears in Collections:Published Articles, Dept. of Cell Physiology and Pharmacology

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