SHPS‐1 negatively regulates integrin αIIbβ3 function through CD47 without disturbing FAK phosphorylation

Kato, Hisashi; Honda, Susumu; Yoshida, Hitoshi; Kashiwagi, Hirokazu; Shiraga, Masamichi; Honma, Nakayuki; Kurata, Yoshiyuki; Tomiyama, Yoshiaki

doi:10.1111/j.1538-7836.2005.01235.x

Cited by 17 publications

(10 citation statements)

References 55 publications

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“…This result is consistent with reports that SIRP-␣ and SIRP-␥ signal through CD47 to regulate hematopoietic cell function, migration, and apoptosis (43)(44)(45)(46) and that SIRP-␣ promotes filopodia formation of CD47-overexpressing neurons (47,48).…”

Section: Sirp-␣ As a Novel Secreted Presynapticsupporting

confidence: 93%

Signal Regulatory Proteins (SIRPS) Are Secreted Presynaptic Organizing Molecules

Umemori

Sanes

2008

Journal of Biological Chemistry

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Neurons transmit information to each other at functional contact sites called synapses. Information transfer involves release of neurotransmitters from synaptic vesicles in nerve terminals, binding of neurotransmitter by receptors at the precisely apposed postsynaptic membrane, and generation of an electrical or chemical signal in the postsynaptic cell. Alterations in synapse number and strength underlie neural plasticity, and defects in synaptic circuitry and function underlie some neurological disorders. Thus, proper assembly of appropriate synapses is essential for optimal functioning of the nervous system (1, 2).Pre-and postsynaptic specializations form in precise apposition to each other at sites where axons contact specific target cells. This precision is one indication that signals are exchanged between presynaptic neurons and postsynaptic target cells to organize synaptic differentiation and maturation (3-5). Several molecules have been identified that function as "synaptic organizers" in cultured neurons, and over the past few years, a few have been shown to function in vivo in the mammalian brain (6 -9). The brain contains dozens if not hundreds of different synaptic types, however, and additional organizers likely remain to be identified.To identify novel synaptic organizers, we devised an assay for presynaptic differentiation in isolated, cultured neurons, and used it to guide biochemical purification of active molecules from brain extracts. In initial studies, we showed that fibroblast growth factor (FGF) 2 22 and its close relatives, FGFs 7 and 10, promote differentiation of neuromuscular and cerebellar synapses (7, 10). Some neuronal populations were unresponsive to these FGFs, however, and FGFs accounted for less than half of the active material in brain extracts. We therefore sought additional active species. Here, we show that SIRP-␣ is a presynaptic organizer.SIRP-␣ (signal regulatory protein ␣; also known as PTPNS1, SHPS1, CD172a, BIT, MFR, and p84) is a transmembrane protein with three immunoglobulin domains (11-14). SIRP-␣ is highly expressed in neurons and myeloid cells, and is concentrated at synapses in the brain (11-18). Its intracellular domain has tyrosine residues that, when phosphorylated, can interact with phosphatases to send negative signals downstream. SIRP-␣ is involved in hematopoietic cell functions such as regulation of host cell phagocytosis and clearance, inflammatory mediator production, and control of cell migration (11-13, 19 -22). Little is known about roles of SIRP-␣ in the nervous system, but it is expressed by hippocampal neurons, promotes neurite outgrowth in culture, and enhances the effect of brainderived neurotrophic factor (23-26). Most of these studies, however, focused on intracellular signals transduced by SIRP-␣ when it is engaged by its ligand, CD47/integrin-associated protein (16). Here, in contrast, we show that the extracellular domain of SIRP-␣ is cleaved and acts as a secreted presynaptic organizer. We also show that two little-studied close relative...

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Section: Sirp-␣ As a Novel Secreted Presynapticsupporting

confidence: 93%

Signal Regulatory Proteins (SIRPS) Are Secreted Presynaptic Organizing Molecules

Umemori

Sanes

2008

Journal of Biological Chemistry

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“…14 Integrin ␣ IIb ␤ 3 activation and ␣-granule secretion of wild-type (WT) and APN-KO platelets were detected by phycoerythrin-conjugated JON/A monoclonal antibody (mAb), which binds specifically to mouse-activated ␣ IIb ␤ 3 (Emfret Analytics) and FITC-conjugated anti-P-selectin mAb (Becton Dickinson), respectively. 14 …”

Section: Platelet Aggregation Study Adhesion Study and Flow Cytometrymentioning

confidence: 99%

Adiponectin Acts as an Endogenous Antithrombotic Factor

Kato¹,

Kashiwagi²,

Shiraga³

et al. 2006

ATVB

Self Cite

168

116

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Objective-Obesity is a common risk factor in insulin resistance and cardiovascular diseases. Although hypoadiponectinemia is associated with obesity-related metabolic and vascular diseases, the role of adiponectin in thrombosis remains elusive. Methods and Results-We investigated platelet thrombus formation in adiponectin knockout (APN-KO) male mice (8 to 12 weeks old) fed on a normal diet. There was no significant difference in platelet counts or coagulation parameters between wild-type (WT) and APN-KO mice. However, APN-KO mice showed an accelerated thrombus formation on carotid arterial injury with a He-Ne laser (total thrombus volume: 13.36Ϯ4.25ϫ10 7 arbitrary units for APN-KO and 6.74Ϯ2.87ϫ10 7 arbitrary units for WT; nϭ10; PϽ0.01). Adenovirus-mediated supplementation of adiponectin attenuated the enhanced thrombus formation. In vitro thrombus formation on a type I collagen at a shear rate of 250 s Ϫ1 , as well as platelet aggregation induced by low concentrations of agonists, was enhanced in APN-KO mice, and recombinant adiponectin inhibited the enhanced platelet aggregation. In WT mice, adenovirus-mediated overexpression of adiponectin additionally attenuated thrombus formation. Key Words: acute coronary syndromes Ⅲ obesity Ⅲ platelets Ⅲ thrombosis O besity is associated with insulin resistance, accelerated atherothrombosis, and cardiovascular diseases. 1,2 Recent studies have revealed that adipose tissue is not only a passive reservoir for energy storage but also produces and secretes a variety of bioactive molecules, known as adipocytokines, including tumor necrosis factor (TNF) ␣, leptin, resistin, and plasminogen activator inhibitor type-1. [2][3][4] Dysregulated production of adipocytokines participates in the development of obesityrelated metabolic and vascular diseases. [2][3][4] Adiponectin is an adipocytokine identified in the human adipose tissue cDNA library, and Acrp30/AdipoQ is the mouse counterpart of adiponectin (reviewed in reference 5 ). Adiponectin, of which mRNA is exclusively expressed in adipose tissue, is a protein of 244 amino acids consisting of 2 structurally distinct domains, an N-terminal collagen-like domain and a C-terminal complement C1q-like globular domain. Adiponectin is abundantly present in plasma (5 to 30 g/mL), and its plasma concentration is inversely related to the body mass index. 5 Plasma adiponectin levels decrease in obesity, type 2 diabetes, and patients with coronary artery disease (CAD). 5-9 Indeed, adiponectin (APN) knockout (KO) mice showed severe diet-induced insulin resistance. 10 In cultured cells, we have demonstrated that human recombinant adiponectin inhibited the expression of adhesion molecules on endothelial cells, the transformation of macrophages to foam cells, and TNF-␣ production from macrophages. 5,11 Furthermore, APN-KO mice showed severe neointimal thickening in mechanically injured arteries. 12 Adenovirusmediated supplementation of adiponectin attenuated the development of atherosclerosis in apolipoprotein E-deficient mice as well as postinj...

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“…20 Platelet counts in platelet-rich plasma (PRP) were adjusted to 3.0 ϫ 10 5 /L by adding platelet-poor plasma (PPP). Aggregation was initiated by addition of acid-insoluble type I collagen (MC Medical) or botrocetin to PRP.…”

Section: Platelet Aggregation Analysismentioning

confidence: 99%

Complete deficiency in ADAMTS13 is prothrombotic, but it alone is not sufficient to cause thrombotic thrombocytopenic purpura

Banno

Kokame

Okuda

et al. 2006

Blood

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146

116

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ADAMTS13 is a plasma metalloproteinase that regulates platelet adhesion and aggregation through cleavage of von Willebrand factor (VWF) multimers. In humans, genetic or acquired deficiency in ADAMTS13 causes thrombotic thrombocytopenic purpura (TTP), a condition characterized by thrombocytopenia and hemolytic anemia with microvascular platelet thrombi. In this study, we report characterization of mice bearing a targeted disruption of the Adamts13 gene. ADAMTS13-deficient mice were born in the expected mendelian distribution; homozygous mice were viable and fertile. Hematologic and histologic analyses failed to detect any evidence of thrombocytopenia, hemolytic anemia, or microvascular thrombosis. However, unusually large VWF multimers were observed in plasma of homozygotes. Thrombus formation on immobilized collagen under flow was significantly elevated in homozygotes in comparison with wild-type mice. Thrombocytopenia was more severely induced in homozygotes than in wild-type mice after intravenous injection of a mixture of collagen and epinephrine. Thus, a complete lack of ADAMTS13 in mice was a prothrombotic state, but it alone was not sufficient to cause TTP-like symptoms. The phenotypic differences of ADAMTS13 deficiencies between humans and mice may reflect differences in hemostatic system functioning in these species. Alternatively, factors in addition to ADAMTS13 deficiency may be necessary for development of TTP. (Blood. 2006;107:3161-3166)

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SHPS‐1 negatively regulates integrin αIIbβ3 function through CD47 without disturbing FAK phosphorylation

Cited by 17 publications

References 55 publications

Signal Regulatory Proteins (SIRPS) Are Secreted Presynaptic Organizing Molecules

Signal Regulatory Proteins (SIRPS) Are Secreted Presynaptic Organizing Molecules

Adiponectin Acts as an Endogenous Antithrombotic Factor

Complete deficiency in ADAMTS13 is prothrombotic, but it alone is not sufficient to cause thrombotic thrombocytopenic purpura

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