Identification of Novel β1 Integrin Binding Sites in the Type 1 and Type 2 Repeats of Thrombospondin-1

Calzada, Marı́a J.; Annis, Douglas S.; Zeng, Bixi; Marcinkiewicz, Cezary; Banas, Bernhard; Lawler, Jack; Mosher, Deane F.; Roberts, D. A.

doi:10.1074/jbc.m406267200

Cited by 85 publications

(80 citation statements)

References 61 publications

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“…Of interest, several of these proteins interact with integrins through their TSR domains. For instance, the TSR domain of thrombospondin-1 is an integrin ligand pan-␤1 specific, and this interaction is crucial for its function (Calzada et al, 2004;Short et al, 2005). Also, the angiogenic inducer CCN1 binds integrin ␣6␤1 by a TSR domain (Leu et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…For instance, mice carrying mutations in integrin ␣6 and those lacking integrin ␤1 show defects in the anchorage of radial glial processes at the meningeal basement membrane in the cerebral and cerebellar cortex (Georges-Labouesse et al, 1998;Graus-Porta et al, 2001;Milner and Campbell, 2002;Belvindrah et al, 2007). On the other hand, integrins interact with the TSR domain of several members of the TSR superfamily (Leu et al, 2003;Calzada et al, 2004;Short et al, 2005). Remarkably, activity-blocking antibodies against integrin ␤1 inhibited the ability of the TSR domains of SCO-spondin to induce neurite outgrowth in vitro (Bamdad et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Polarized expression of integrin β1 in diencephalic roof plate during chick development, a possible receptor for SCO‐spondin

Caprile

Osorio

Henríquez

et al. 2009

Developmental Dynamics

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The roof plate of the caudal diencephalon is formed by the posterior commissure (PC) and the underlying secretory ependyma, the subcommissural organ (SCO). The SCO is composed by radial glial cells bearing processes that cross the PC and attach to the meningeal basement membrane. Since early development, the SCO synthesizes SCO-spondin, a glycoprotein that shares similarities to axonal guidance proteins. In vitro, SCO-spondin promotes neuritic outgrowth through a mechanism mediated by integrin ␤1. However, the secretion of SCO-spondin toward the extracellular matrix that surrounds the PC axons and the expression of integrins throughout PC development have not been addressed. Here we provide immunohistochemical evidence to suggest that during chick development SCO cells secrete SCO-spondin through their basal domain, where it is deposited into the extracellular matrix in close contact with axons of the PC that express integrin ␤1. Our results suggest that SCO-spondin has a role in the development of the PC through its interaction with integrin ␤1.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polarized expression of integrin β1 in diencephalic roof plate during chick development, a possible receptor for SCO‐spondin

Caprile

Osorio

Henríquez

et al. 2009

Developmental Dynamics

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“…7B and results not shown). Although TSP1 is a ligand for some of these integrins (43,44), the binding affinities are too low for direct competition by 2.2 nM TSP1 to account for the observed inhibition.…”

Section: Thrombospondin-1 Inhibits Myristate Uptake Via Cd36mentioning

confidence: 98%

Thrombospondin-1 Inhibits Nitric Oxide Signaling via CD36 by Inhibiting Myristic Acid Uptake

Isenberg

Jia

Fukuyama

et al. 2007

Journal of Biological Chemistry

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123

110

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Although CD36 is generally recognized to be an inhibitory signaling receptor for thrombospondin-1 (TSP1), the molecular mechanism for transduction of this signal remains unclear. Based on evidence that myristic acid and TSP1 each modulate endothelial cell nitric oxide signaling in a CD36-dependent manner, we examined the ability of TSP1 to modulate the fatty acid translocase activity of CD36. TSP1 and a CD36 antibody that mimics the activity of TSP1 inhibited myristate uptake. Recombinant TSP1 type 1 repeats were weakly inhibitory, but an anti-angiogenic peptide derived from this domain potently inhibited myristate uptake. This peptide also inhibited membrane translocation of the myristoylated CD36 signaling target Fyn and activation of Src family kinases. Myristate uptake stimulated cGMP synthesis via endothelial nitric-oxide synthase and soluble guanylyl cyclase. CD36 ligands blocked myristate-stimulated cGMP accumulation in proportion to their ability to inhibit myristate uptake. TSP1 also inhibited myristate-stimulated cGMP synthesis by engaging its receptor CD47. Myristate stimulated endothelial and vascular smooth muscle cell adhesion on type I collagen via the NO/cGMP pathway, and CD36 ligands that inhibit myristate uptake blocked this response. Therefore, the fatty acid translocase activity of CD36 elicits proangiogenic signaling in vascular cells, and TSP1 inhibits this response by simultaneously inhibiting fatty acid uptake via CD36 and downstream cGMP signaling via CD47. Pathological angiogenesis or the lack thereof underlies a number of major diseases (1). Proangiogenic signals from vascular endothelial growth factors (VEGF)2 and fibroblast growth factors (FGF1 and FGF2) to induce blood vessel formation are opposed by signals from endogenous angiogenesis inhibitors, including two thrombospondins (TSP1 and TSP2) and proteolytic fragments of several extracellular matrix components (2, 3). Defining the mechanism of action of these inhibitors has been complicated by the finding that vascular cells express multiple receptors for several of these molecules. In the case of TSP1, endothelial cells express at least eight receptors, and some of these elicit pro-rather than anti-angiogenic responses (4, 5). The activities of some TSP1 receptors differ between large vessel and microvascular endothelial cells, and some are regulated by specific contextual signals (4 -6). CD36, a member of the scavenger receptor B family, is a TSP1 receptor that is selectively expressed in microvascular endothelium (7,8). CD36 was initially reported to recognize CSVTCG sequences in the type 1 repeats of TSP1 (9), but further studies identified higher affinity binding to the adjacent GVQXR sequences in the second and third type 1 repeats (10, 11). CD36 binding was markedly enhanced by epimerization of the first Ile in a peptide from the second type 1 repeat 434 GDGVITRIR 442 , where I (Ile) is the D isomer (11). TSP1, recombinant type 1 repeats of TSP1, and peptide mimetics of its CD36 binding sequences inhibit FGF2-stimulated endo...

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“…The TSRs mediate interactions of THBS-1 with CD36 and integrins [24][25][26]. CD36 has been shown to mediate the anti-angiogenic activity of the TSRs [27].…”

Section: Functional Sitesmentioning

confidence: 99%

Thrombospondins: from structure to therapeutics

Carlson

Lawler

Mosher

2008

Cell. Mol. Life Sci.

168

111

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Thrombospondins are large secreted, multi-modular, calcium-binding glycoproteins that have complex roles in mediating cellular processes. Determination of high-resolution structures of thrombospondins has revealed unique and interesting protein motifs. Here, we review this progress and discuss implications for function. By combining structures of modules from thrombospondins and related extracellular proteins it is now possible to prepare an overall model of the structure of thrombospondin-1 and thrombospondin-2 and discern features of other thrombospondins. (Part of a multi-author Review) KeywordsThrombospondin; extracellular protein structure; cartilage oligomeric matrix protein; calcium

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Identification of Novel β1 Integrin Binding Sites in the Type 1 and Type 2 Repeats of Thrombospondin-1

Cited by 85 publications

References 61 publications

Polarized expression of integrin β1 in diencephalic roof plate during chick development, a possible receptor for SCO‐spondin

Polarized expression of integrin β1 in diencephalic roof plate during chick development, a possible receptor for SCO‐spondin

Thrombospondin-1 Inhibits Nitric Oxide Signaling via CD36 by Inhibiting Myristic Acid Uptake

Thrombospondins: from structure to therapeutics

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