The interaction of Thrombospondins with extracellular matrix proteins

Abstract

The thrombospondins (TSPs) are a family of five matricellular proteins that appear to function as adapter molecules to guide extracellular matrix synthesis and tissue remodeling in a variety of normal and disease settings. Various TSPs have been shown to bind to fibronectin, laminin, matrilins, collagens and other extracellular matrix (ECM) proteins. The importance of TSP-1 in this context is underscored by the fact that it is rapidly deposited at the sites of tissue damage by platelets. An association of TSPs with collagens has been known for over 25 years. The observation that the disruption of the TSP-2 gene in mice leads to collagen fibril abnormalities provided important in vivo evidence that these interactions are physiologically important. Recent biochemical studies have shown that TSP-5 promotes collagen fibril assembly and structural studies suggest that TSPs may interact with collagens through a highly conserved potential metal ion dependent adhesion site (MIDAS). These interactions are critical for normal tissue homeostasis, tumor progression and the etiology of skeletal dysplasias.

Supporting Roles of Platelet Thrombospondin-1 and CD36 in Thrombus Formation on Collagen

“…[16][17][18] In addition to CD36, several other platelet receptors for TSP1 have been proposed. These include the glycoprotein Ib-V-IX complex [19][20][21] and glycoprotein CD47.…”

Pneumococcal Adhesins PavB and PspC Are Important for the Interplay with Human Thrombospondin-1

“…In this scenario the interaction of bacterial surface adhesins with soluble host proteins, host cellular receptors, or components of the ECM represents the major strategy essential to achieve a stable colonization (10,11). The epithelial ECM comprises the interstitial matrix between cells and the basal lamina upon the epithelial layer, which is composed of proteoglycans and fibrous proteins (among others fibronectin, collagen, elastins, and laminins) as well as matricellular proteins like vitronectin (Vn) or hTSP-1 (12)(13)(14)(15)(16).…”

Extracellular matrix-mediated cellular communication in the heart

“…TSP bind to cell surface receptors, such as integrins, CD36, and CD47 [123–126], modulating cell-ECM interactions, including focal adhesions [127, 128] (Figure 2). Although these matricellular proteins are not detectable in normal adult ECM, their expression increases greatly in response to cardiac injury [129–131] and participate in heart failure progression [132]. The TSP family consists of five members subdivided based on their structural organization and oligomerization status; TSP-1,-2 form trimers and -3, -4 and -5 form pentamers.…”