Ligand-binding specificities of laminin-binding integrins: A comprehensive survey of laminin–integrin interactions using recombinant α3β1, α6β1, α7β1 and α6β4 integrins

Nishiuchi, Ryoko; Takagi, Junichi; Hayashi, Maria; Ido, Hiroyuki; Yagi, Yoshiko; Sanzen, Noriko; Tsuji, Tsutomu; Yamada, Masashi; Sekiguchi, Kiyotoshi

doi:10.1016/j.matbio.2005.12.001

Cited by 338 publications

(358 citation statements)

References 46 publications

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“…Although laminin-111 is not expressed in normal or dystrophic adult skeletal muscle, studies indicate it is a preferred ligand for ␣ 7 ␤ 1 -integrin (21,22). Treatment with laminin-111 stabilized the sarcolemma of mdx skeletal muscle, reduced myofiber degeneration, decreased serum creatine kinase, and protected muscle from exercise-induced injury, suggesting that treatment with laminin-111 may be a potent therapy for DMD.…”

Section: Discussionmentioning

confidence: 99%

Laminin-111 protein therapy prevents muscle disease in the mdx mouse model for Duchenne muscular dystrophy

Rooney¹,

Gurpur²,

Burkin

2009

Proc. Natl. Acad. Sci. U.S.A.

116

109

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Duchenne muscular dystrophy (DMD) is a devastating neuromuscular disease caused by mutations in the gene encoding dystrophin. Loss of dystrophin results in reduced sarcolemmal integrity and increased susceptibility to muscle damage. The α 7 β 1 -integrin is a laminin-binding protein up-regulated in the skeletal muscle of DMD patients and in the mdx mouse model. Transgenic overexpression of the α 7 -integrin alleviates muscle disease in dystrophic mice, making this gene a target for pharmacological intervention. Studies suggest laminin may regulate α 7 -integrin expression. To test this hypothesis, mouse and human myoblasts were treated with laminin and assayed for α 7 -integrin expression. We show that laminin-111 (α 1 , β 1 , γ 1 ), which is expressed during embryonic development but absent in normal or dystrophic skeletal muscle, increased α 7 -integrin expression in mouse and DMD patient myoblasts. Injection of laminin-111 protein into the mdx mouse model of DMD increased expression of α 7 -integrin, stabilized the sarcolemma, restored serum creatine kinase to wild-type levels, and protected muscle from exercised-induced damage. These findings demonstrate that laminin-111 is a highly potent therapeutic agent for the mdx mouse model of DMD and represents a paradigm for the systemic delivery of extracellular matrix proteins as therapies for genetic diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Laminin-111 protein therapy prevents muscle disease in the mdx mouse model for Duchenne muscular dystrophy

Rooney¹,

Gurpur²,

Burkin

2009

Proc. Natl. Acad. Sci. U.S.A.

116

109

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“…Recombinant GRP78 (StressMarq Biosciences Inc., Victoria, BC, Canada) was pre-coated onto 96-well plate and saturation binding with increasing concentrations of rISM were carried out. 49 K d was calculated using GraphPad Prism (GraphPad Software Inc., La Jolla, CA, USA). Quantification of cell-surface GRP78 and integrin avb5 molecule numbers.…”

Section: Methodsmentioning

confidence: 99%

Isthmin targets cell-surface GRP78 and triggers apoptosis via induction of mitochondrial dysfunction

Zhang

et al. 2014

Cell Death Differ

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Isthmin (ISM) is a secreted 60-kDa protein that potently induces endothelial cell (EC) apoptosis. It suppresses tumor growth and angiogenesis in mice when stably overexpressed in cancer cells. Although avb5 integrin serves as a low-affinity receptor for ISM, the mechanism by which ISM mediates antiangiogenesis and apoptosis in ECs remain to be fully resolved. In this work, we report the identification of cell-surface glucose-regulated protein 78 kDa (GRP78) as a high-affinity receptor for ISM (K d ¼ 8.6 nM). We demonstrated that ISM-GRP78 interaction triggers apoptosis not only in activated ECs but also in cancer cells expressing high level of cell-surface GRP78. Normal cells and benign tumor cells tend to express low level of cell-surface GRP78 and are resistant to ISM-induced apoptosis. Upon binding to GRP78, ISM is internalized into ECs through clathrin-dependent endocytosis that is essential for its proapoptotic activity. Once inside the cell, ISM co-targets with GRP78 to mitochondria where it interacts with ADP/ATP carriers on the inner membrane and blocks ATP transport from mitochondria to cytosol, thereby causing apoptosis. Hence, ISM is a novel proapoptotic ligand that targets cell-surface GRP78 to trigger apoptosis by inducing mitochondrial dysfunction. The restricted and high-level expression of cell-surface GRP78 on cancer cells and cancer ECs make them uniquely susceptible to ISM-targeted apoptosis. Indeed, systemic delivery of recombinant ISM potently suppressed subcutaneous 4T1 breast carcinoma and B16 melanoma growth in mice by eliciting apoptosis selectively in the cancer cells and cancer ECs. Together, this work reveals a novel ISM-GRP78 apoptosis pathway and demonstrates the potential of ISM as a cancer-specific and dual-targeting anticancer agent.

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“…The interaction between Laminin-332 and the a6b4 integrin in hemidesmosome (HD) assembly merits special note and is discussed ahead. The LG1-3 domain cluster, located at the end of the long arm of different laminins, provide what is thought as the principal integrininteraction sites, binding to a6b1, a6b4, a7b1, and a3b1 (Nishiuchi et al 2006). Genetic analysis with laminin-class integrin subunit-deficient mice has revealed the importance of the LG domain integrin subunits for tissue and organ morphogenesis, including epidermal/ dermal attachment, brain development, and glomerular and lung development (GeorgesLabouesse et al 1996;Kreidberg et al 1996;Di Persio et al 1997;Mayer et al 1997;GeorgesLabouesse et al 1998).…”

Section: Integrin Interactionsmentioning

confidence: 99%

“…Laminins differ based on their complement of domains, ability to polymerize, proteolytic processing, receptor-binding repertoire, and receptor affinities. Relative strong (heavy solid and dashed lines) and weak (thin dashed lines) interactions are indicated with heavy and thin lines with approximate dissociation constants are indicated where known (small numbers in nM values) (Denzer et al 1998;Gesemann et al 1998;Hopf et al 1999;Talts et al 1999;Talts et al 2000;Hopf et al 2001;Nielsen and Yamada 2001;Ries et al 2001;Garbe et al 2002;Smirnov et al 2002;Nishiuchi et al 2006;Harrison et al 2007). …”

Section: Basement Membranesmentioning

confidence: 99%

“…The laminin-specific a6b4 integrin has an unusually long b-subunit tail that allows it to bind to HD plectin that links keratin. In the basement membrane zone, a bond is formed among laminin-332 and type VII collagen of the stromal anchoring fibrils (Rousselle et al 1997;Litjens et al 2006;Nishiuchi et al 2006). Thus laminin 332 forms a crucial link among the cell HD and the stromal anchoring fibrils.…”

Section: Epidermal-dermal Junction: Stable Adhesion and Cell Migrationmentioning

confidence: 99%

See 1 more Smart Citation

Basement Membranes: Cell Scaffoldings and Signaling Platforms

Yurchenco

2010

Cold Spring Harbor Perspectives in Biology

769

775

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Ligand-binding specificities of laminin-binding integrins: A comprehensive survey of laminin–integrin interactions using recombinant α3β1, α6β1, α7β1 and α6β4 integrins

Cited by 338 publications

References 46 publications

Laminin-111 protein therapy prevents muscle disease in the mdx mouse model for Duchenne muscular dystrophy

Laminin-111 protein therapy prevents muscle disease in the mdx mouse model for Duchenne muscular dystrophy

Isthmin targets cell-surface GRP78 and triggers apoptosis via induction of mitochondrial dysfunction

Basement Membranes: Cell Scaffoldings and Signaling Platforms

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