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Agrin (0):
Recent article
Agrin
Laboratory Investigation (90)11 2010
Abstract
We investigated the involvement of dystrophin-associated proteins (DAPs) and their relationship with the perivascular basement membrane in the brains of mdx mice and controls at the age of 2 months. We analyzed (1) the expression of glial DAPs α-β-dystroglycan (DG), α-syntrophin, aquaporin-4 (AQP...
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PMID: 20714324
PDF is available here.
PDF is available here.
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Experimental Cell Research (316)14 2010
Abstract
We investigated the role of agrin's glycosaminoglycan (GAG) chains in the induction of filopodia formation by TM-agrin over-expression in hippocampal neurons, and in the induction of filopodia-like processes in COS7 cells. Deletion of the GAG chains of TM-agrin sharply reduced formation of filopodia...
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PMID: 20471381
PDF is available here.
PDF is available here.
Abstract
We show that similar processes can be induced by overexpression of transmembrane-agrin in several non-neuronal cell lines. Mapping of the process-inducing activity in neurons and non-neuronal cells demonstrates that the cytoplasmic part of transmembrane agrin is dispensable and that the extracellula...
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PMID: 19940118
PDF is available here.
PDF is available here.
Journal of UOEH (31)3 2009
Abstract
These results show that the major form of agrin expressed in the brain microvessels is of basal lamina-associated LN agrin and suggest that LN agrin may play a role in molecular organization at the interface between the parenchyma cells and microvessels....
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PMID: 19750929
PDF is available here.
PDF is available here.
Abstract
Abstract
We show that both synaptic and extrasynaptic forms of laminin and agrin have increased binding to the CT carbohydrate compared to sialyl-N-acetyllactosamine, its extrasynaptically expressed precursor. Muscle laminins also show increased binding to CT-glycosylated muscle alpha dystroglycan relative t...
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PMID: 19442736
PDF is available here.
PDF is available here.
Abstract
These findings cast further doubt upon a critical role for the GBM in charge selectivity....
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PMID: 19144998
PDF is available here.
PDF is available here.
Neuromuscular Disorders (19)5 2009
Abstract
We show that the formation and maintenance of neuromuscular junctions in Large(myd) mice are greatly compromised. Neuromuscular junctions are not confined to the muscle endplate zone but are widely spread and are frequently accompanied by exuberant nerve sprouting. Nerve terminals are highly fragmen...
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PMID: 19346129
PDF is available here.
PDF is available here.
Brain Research (1260) 2009
Abstract
We investigated if Abeta may influence production and expression of two major Abeta-associated HSPG species, agrin and glypican-1. When human brain pericytes (HBP) were cultured in the presence of Abeta, protein and mRNA expression of both agrin and glypican-1 were increased and more radioactive sul...
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PMID: 19166823
PDF is available here.
PDF is available here.
Abstract
We tested the hypothesis that agrin induces a change in the excitability properties in primary cultures of non-innervated human myotubes. Electrical membrane properties of human myotubes were recorded using the whole-cell patch-clamp technique. Cell incubation with recombinant chick neural agrin (1...
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PMID: 18807173
PDF is available here.
PDF is available here.
Abstract
We report a hybrid approach for recognizing calcium-binding sites in disordered regions. Our approach combines loop modeling with a machine learning method (FEATURE) for structure-based site recognition. For validation, we compared the performance of our method on known calcium-binding sites for whi...
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PMID: 20003365
PDF is available here.
PDF is available here.
Abstract
Basement membranes are sheet-like cell-adherent extracellular matrices that serve as cell substrata and solid-phase agonists, contributing to tissue organization, stability and differentiation. These matrices are assembled as polymers of laminins and type IV collagens that are tethered to nidogens a...
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PMID: 19355968
PDF is available here.
PDF is available here.
Abstract
We demonstrate that Wnt signaling is necessary for the formation of acetylcholine receptor (AChR) clusters without affecting muscle growth. Similarly, diaphragms from Dishevelled-1 mutant mice with deficiency in Wnt signaling exhibit defects in cluster distribution. In cultured myotubes, Wnt3 increa...
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PMID: 19020093
PDF is available here.
PDF is available here.
Magyar Onkológia (52)4 2008
Abstract
We propose that agrin IHC might help distinguish between malignant hepatocellular lesions and their benign mimickers....
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PMID: 19068466
PDF is available here.
PDF is available here.
Abstract
Two recent papers reported identification of a long-sought agrin coreceptor, Lrp4 (Kim et al. in Cell and Zhang et al. in Neuron). In this issue of Neuron, Linnoila et al. report the identification of a new player in the agrin-MuSK pathway, Tid1, which directly interacts with MuSK an...
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PMID: 19038209
PDF is available here.
PDF is available here.
Abstract
We used two-hybrid screens to identify a protein, tumorous imaginal discs (Tid1), that binds to the cytoplasmic domain of muscle-specific kinase (MuSK), a major component of the agrin receptor. Like MuSK, Tid1 colocalizes with AChRs at developing, adult, and denervated motor endplates. Knockdown of...
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PMID: 19038220
PDF is available here.
PDF is available here.
Abstract
We demonstrate that agrin is O-fucosylated in a Pofut1-dependent manner, and that this glycosylation can regulate agrin function. Fucosylation of recombinant C45 agrin, both active (neural, z8) and inactive (muscle, z0) splice forms, was eliminated when agrin was overexpressed in Pofut1-deficient ce...
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PMID: 18775496
PDF is available here.
PDF is available here.
Abstract
We report that LRP4, a low-density lipoprotein receptor (LDLR)-related protein, is expressed specifically in myotubes and binds to neuronal agrin. Its expression enables agrin binding and MuSK signaling in cells that otherwise do not respond to agrin. Suppression of LRP4 expression in muscle cells a...
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PMID: 18957220
PDF is available here.
PDF is available here.
Abstract
We report that Lrp4, a member of the LDLR family, is a receptor for Agrin, forms a complex with MuSK, and mediates MuSK activation by Agrin....
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PMID: 18848351
PDF is available here.
PDF is available here.
Journal of Neuroscience (28)39 2008
Abstract
We have shown previously that Schwann cell-conditioned medium (SC-CM) promotes synaptogenesis in Xenopus nerve-muscle cocultures. The present study aimed to identify the synaptogenic molecules in SC-CM. Combining biochemical approaches and in vitro bioassays, we found that SC-CM contains transformin...
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PMID: 18815246
PDF is available here.
PDF is available here.
Biophysical Journal (95)6 2008
Abstract
We used a microfluidic device to focally deliver agrin to protosynaptic AChR clusters in micropatterned myotube cultures. The distribution of AChRs labeled with fluorescent bungarotoxin was imaged at various time points over >24 h. We find that a 4-h focal application of agrin (100 nM) preferentiall...
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PMID: 18502803
PDF is available here.
PDF is available here.
Neuroscience Letters (442)3 2008
Abstract
We studied the effects of repetitive applications of neuronal agrin to primary hippocampal cell culture on nicotine-induced phosphorylated cyclic AMP response element-binding protein (pCREB) expression, a marker of neuroadaptation, by using immunofluorescence-based assessment of pCREB-positive neuro...
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PMID: 18639611
PDF is available here.
PDF is available here.
Abstract
We show that a miniaturized form of agrin, consisting of the laminin-binding and MuSK-activating domains, is sufficient to fully restore NMJs in agrin mutant mice when expressed by developing muscle. Although miniagrin is expressed uniformly throughout muscle fibers and induces ectopic AChR clusters...
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PMID: 18685098
PDF is available here.
PDF is available here.
Abstract
During adolescence there is a loss of approximately 30% of the synapses formed in the cortex during childhood. Comprehensive studies of the visual cortex show that this loss of synapses does not occur as a consequence of less appropriate projections being eliminated in favour of more appropriate one...
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PMID: 18622774
PDF is available here.
PDF is available here.
Abstract
Attention has focused on glomerular basement membrane heparan sulfate proteoglycans, long considered primary charge barrier components. Agrin contributes significantly to glomerular basement membrane charge but, like perlecan and collagen XVIII, is dispensable for glomerular structure and function....
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PMID: 18660676
PDF is available here.
PDF is available here.
Journal of Neurotrauma (25)7 2008
Abstract
We documented that matrix metalloproteinase 3 (MMP-3) expression and activity increase following traumatic brain injury (TBI). We now report protein and mRNA analysis of agrin, a MMP-3 substrate, over the time course of trauma-induced synaptogenesis. Agrin expression during the successful synaptic r...
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PMID: 18627255
PDF is available here.
PDF is available here.
Abstract
Shortly after encountering the muscle surface, the motor axon releases agrin to the postsynaptic muscle membrane to regulate postsynaptic differentiation. Neural agrin activates postsynaptic muscle-specific kinase to induce aggregation of muscle nicotinic acetylcholine receptors (nAChR) expressed th...
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PMID: 18649634
PDF is available here.
PDF is available here.
Neuroscience (154)2 2008
Abstract
We established a primary muscle cell culture system from alphaDB knockout mice and stably expressed individual alphaDB isoforms using retroviral infection. A comparison between wild-type and alphaDB knockout muscle cells showed that in the absence of alphaDB, fewer AChR clusters formed in response t...
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PMID: 18468804
PDF is available here.
PDF is available here.
FASEB Journal (22)6 2008
Abstract
We present a detailed biochemical analysis of neurotrypsin-mediated agrin cleavage in the murine brain. In brain homogenates, we found that neurotrypsin exclusively cleaves glycanated variants of agrin. Studies with isolated synaptosomes obtained by subcellular fractionation from brains of wild-type...
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PMID: 18230682
PDF is available here.
PDF is available here.
Abstract
We have analyzed retina development in agrin morphants. Retinal differentiation is impaired in agrin morphants, with retinal lamination being disrupted following agrin morpholino treatment. Pax 6.1 and Mbx1 gene expression, markers of eye development, are markedly reduced in agrin morphants. Formati...
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PMID: 18327763
PDF is available here.
PDF is available here.
Abstract
Basement membranes lie at the epithelial-mesenchymal interface of most tissues. These thin layers of highly specialized extracellular matrix vary in composition in different tissues and also over the course of tissue morphogenesis. Heparan sulfate proteoglycans, which were originally identified in b...
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PMID: 18291521
PDF is available here.
PDF is available here.
Journal of Neuroscience (28)7 2008
Abstract
We demonstrated that MuSK became rapidly internalized in response to agrin, which appeared to be required for induced AChR clustering. Moreover, we provided evidence for a role of N-ethylmaleimide sensitive factor (NSF) in regulating MuSK endocytosis and subsequent signaling in response to agrin sti...
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PMID: 18272689
PDF is available here.
PDF is available here.
Abstract
We compared the establishment of the excitation-contraction coupling mechanism in myotubes differentiated in four different experimental paradigms: 1) aneurally cultured, 2) cocultured with fetal rat spinal cord explants, 3) aneurally cultured in medium conditioned by cocultures, and 4) aneurally cu...
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PMID: 18003748
PDF is available here.
PDF is available here.
Biotechnology Advances (26)3 2008
Abstract
We review the diverse temporal and spatial expression patterns and functions of these molecules and the impact that dysregulation may have on a number of disease states. Many know agrin as a modulator of synaptogenesis and the neuregulins for their prominent role in breast cancer; this review elabor...
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PMID: 18222620
PDF is available here.
PDF is available here.
Nature Neuroscience (11)1 2008
Abstract
We show that expression of Musk is prepatterned in muscle and that early Musk expression in developing myotubes is sufficient to establish muscle prepatterning. We further show that ectopic Musk expression promotes ectopic synapse formation, indicating that muscle prepatterning normally has an instr...
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PMID: 18084289
PDF is available here.
PDF is available here.
BMC Cell Biology (9)1 2008
Abstract
Here we show a similar dependence of cell adhesion on the spacing of agrin, a protein that exists as both a secreted, matrix-bound form and a type-2 transmembrane form in vivo. Agrin was presented as a substrate for cell adhesion assays by anchoring recombinant protein to gold nanoparticles that wer...
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PMID: 19055842
PDF is available here.
PDF is available here.
Zhongguo Xiufu Chongjian Waike Zazhi/Chinese Journal of Reparative and Reconstructive Surgery (22)1 2008
Abstract
The Annexin V and Agrin were special substances of sensory and motor nerves respectively and can act as specific antigens for identifying different nerve fascicles. There were significant differences in the intensity and breadth of the peak of the spectral properties between motor and sensory fascic...
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PMID: 18361245
PDF is available here.
PDF is available here.
Abstract
We examined the temporal expression of cell adhesion molecules (CAMs) in synaptosomes after transient middle cerebral artery occlusion (MCAO) in mice. We focused on events preceding the onset of ischemic neuronal cell death (<48 h). Synaptosome preparations were enriched in synaptically localized pr...
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PMID: 17519975
PDF is available here.
PDF is available here.
Journal of Immunology (179)11 2007
Abstract
These results demonstrate that agrin expression in human T cells is regulated by cell activation and IFN-alpha, and may have an important function during cell activation with potential implications for autoimmunity....
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PMID: 18025246
PDF is available here.
PDF is available here.
Neuroscience (149)3 2007
Abstract
We analyzed the morphological and molecular changes induced by agrin in growth cones of hippocampal neurons that developed in culture. Morphometric analysis showed a significant enlargement of growth cones of hippocampal neurons cultured in the presence of agrin. These agrin-induced growth cone chan...
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PMID: 17870250
PDF is available here.
PDF is available here.
FASEB Journal (21)13 2007
Abstract
We describe the biochemical characterization of neurotrypsin and its so far unique substrate agrin. In cell culture experiment as well as in neurotrypsin-deficient mice, we showed that agrin cleavage depends on neurotrypsin and occurs at two conserved sites. Neurotrypsin and agrin were expressed rec...
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PMID: 17586728
PDF is available here.
PDF is available here.
Human Pathology (38)10 2007
Abstract
We aimed to study the mRNA and protein expression of agrin in cholangiocarcinoma (CC) and focused on the differences between CC and hepatocellular carcinoma (HCC). Eighty surgically removed liver specimens were studied by immunohistochemistry. Representative samples were used for immunoblotting. mRN...
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PMID: 17640714
PDF is available here.
PDF is available here.
Abstract
We describe effects of agrin on the expression and distribution of the water channel protein aquaporin-4 (AQP4) and on the swelling capacity of cultured astrocytes of newborn mice. If astrocytes were cultured on a substrate containing poly DL-ornithine, anti-AQP4 immunoreactivity was evenly and diff...
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PMID: 17927773
PDF is available here.
PDF is available here.
Biochemistry (Washington) (46)33 2007
Abstract
We found that agrin-G3 binds sialic acid in a Ca2+-dependent manner. ITC data indicate that binding is exothermic and occurs with a 1:1 stoichiometry. NMR chemical shift changes map the sialic acid binding site to the loops that control the domain's acetylcholine receptor clustering activity. By con...
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PMID: 17649979
PDF is available here.
PDF is available here.
Toxicology In Vitro (21)5 2007
Abstract
We studied the effect of the estrogenic pesticide methoxychlor (MXC) on skeletal muscle development using C2C12 cell culture. Myoblast cultures were exposed to various concentrations of MXC at various times during the process of myoblast fusion into myotubes. We observed that MXC exposure decreased...
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PMID: 17314029
PDF is available here.
PDF is available here.
Developmental Biology (307)2 2007
Abstract
We show that GC and PKG are important for agrin signaling at the embryonic NMJ of the frog, Xenopus laevis. Inhibitors of both GC and PKG reduced endogenous AChR aggregation in embryonic muscles by 50-85%, and blocked agrin-induced AChR aggregation in cultured embryonic muscle cells. A cyclic GMP an...
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PMID: 17560564
PDF is available here.
PDF is available here.
Abstract
We show that calpain, a calcium-dependent protease, is activated by the cholinergic stimulation and is required for induced dispersion of AChR clusters. Interestingly, the AChR-associated protein rapsyn interacted with calpain in an agrin-dependent manner, and this interaction inhibited the protease...
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PMID: 17640526
PDF is available here.
PDF is available here.
Abstract
We conclude that agrin is not required for establishment or maintenance of GBM architecture. Although agrin contributes significantly to the anionic charge to the GBM, both it and its charge are not needed for glomerular permselectivity. This calls into question whether charge selectivity is a featu...
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PMID: 17591961
PDF is available here.
PDF is available here.
Abstract
We show that overexpression of the cytotoxic T cell (CT) GalNAc transferase (Galgt2) is effective in inhibiting the development of muscle pathology in the dy(W) mouse model of MDC1A, much as we had previously shown in mdx animals. Embryonic overexpression of Galgt2 in skeletal muscles using transgen...
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PMID: 17591965
PDF is available here.
PDF is available here.
Journal of Neuroscience (27)27 2007
Abstract
We examined the role of agrin at brain synapses. We show that agrin is associated with excitatory but not inhibitory synapses in the cerebral cortex. Most importantly, we examined the brains of agrin-deficient mice whose perinatal death was prevented by the selective expression of agrin in motor neu...
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PMID: 17611272
PDF is available here.
PDF is available here.
Abstract
We report the analysis of an uncharacterized fourth Shc family protein, ShcD/Shc4, that is expressed in adult brain and skeletal muscle. Consistent with this expression pattern, we find that ShcD can associate via its PTB domain with the phosphorylated muscle-specific kinase (MuSK) receptor tyrosine...
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PMID: 17452444
PDF is available here.
PDF is available here.
Abstract
We show that upon experimental and human renal ischemia/reperfusion, associated with severe endothelial damage, microvascular basement membrane (BM) heparan sulfate proteoglycans (HSPGs) are modified to bind L-selectin and monocyte chemoattractant protein-1. In an in vitro rolling and adhesion assay...
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PMID: 17525255
PDF is available here.
PDF is available here.
Journal of Neurochemistry (101)6 2007
Abstract
We demonstrate that peripheral nerve myelination is defective in the fukutin-deficient chimeric mice, a mouse model of Fukuyama-type congenital muscular dystrophy, which is the most common alpha-dystroglycanopathy in Japan. In the peripheral nerve of these mice, the density of myelinated nerve fiber...
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PMID: 17326765
PDF is available here.
PDF is available here.
Abstract
We found that agrin acts as one such synaptogenic factor at neuronal synapses in the PNS by demonstrating that structural synapse formation is impaired in the superior cervical ganglia (SCG) of z+ agrin-deficient mice and in SCG cultures derived from those animals. Here, we tested whether synaptic f...
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PMID: 17443806
PDF is available here.
PDF is available here.
Abstract
We found that agrin acts as one such synaptogenic factor at neuronal synapses in the PNS by demonstrating that structural synapse formation is impaired in the superior cervical ganglia (SCG) of z+ agrin-deficient mice and in SCG cultures derived from those animals. Here, we tested whether synaptic f...
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PMID: 17443806
PDF is available here.
PDF is available here.
Abstract
We examined the early postnatal development of agrin-deficient mice in which perinatal death was prevented by transgenic expression of neural agrin in motor neurons. Such transgenic, agrin-deficient mice were born at Mendelian ratio but exhibited severe postnatal growth retardation. Growth plate mor...
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PMID: 17186266
PDF is available here.
PDF is available here.
Journal of Cell Biology (176)7 2007
Abstract
We have previously shown in mouse models for MDC1A that muscle-specific overexpression of a miniaturized form of agrin (mini-agrin), which binds to dystroglycan but not to alpha7beta1 integrin, substantially ameliorates the disease (Moll, J., P. Barzaghi, S. Lin, G. Bezakova, H. Lochmuller, E. Engva...
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PMID: 17389231
PDF is available here.
PDF is available here.
Developmental Biology (303)1 2007
Defects in eye development in transgenic mice overexpressing the heparan sulfate proteoglycan agrin.
Abstract
We establish that transgenic mice overexpressing the HSPG agrin have severe ocular dysgenesis. The defects occur through a gain-of-function mechanism and penetrance is dependent on agrin dosage. The agrin-induced developmental defects are highly variable, and include anophthalmia, persistence of vit...
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PMID: 17196957
PDF is available here.
PDF is available here.
Journal of Cell Science (120)Pt 5 2007
Abstract
We present evidence that laminin-induced AChR clustering is mediated by the activation of the Rho GTPases Cdc42, Rac and Rho. Clustering in response to laminin is blocked by the dominant negative mutants Cdc42N17, RacN17 and RhoN19, as well as by the Rho inhibitor C3 transferase. Moreover, laminin-i...
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PMID: 17298982
PDF is available here.
PDF is available here.
Glycobiology (17)2 2007
Abstract
Although recent studies have extended our understanding of agrin's function during development, its function in the central nervous system (CNS) is not clearly understood. To address this question, zebrafish agrin was identified and characterized. Zebrafish agrin is expressed in the developing CNS a...
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PMID: 17110391
PDF is available here.
PDF is available here.