18 results match your criteria agrin consisting

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Three-Dimensional Human Neural Stem Cell Models to Mimic Heparan Sulfate Proteoglycans and the Neural Niche.

Semin Thromb Hemost 2021 Apr 1;47(3):308-315. Epub 2021 Apr 1.

Genomics Research Centre, Stem Cell and Neurogenesis Group, Centre for Genomics and Personalised Health, School of Biomedical Science, Queensland University of Technology, Kelvin Grove, Queensland, Australia.

Heparan sulfate proteoglycans (HSPGs) are a diverse family of polysaccharides, consisting of a core protein with glycosaminoglycan (GAG) side chains attached. The heterogeneous GAG side-chain carbohydrates consist of repeating disaccharides, with each side chain possessing a specific sulfation pattern. It is the variable sulfation pattern that allows HSPGs to interact with numerous ligands including growth factors, cytokines, chemokines, morphogens, extracellular matrix (ECM) glycoproteins, collagens, enzymes, and lipases. Read More

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Pelvic floor muscle function recovery using biofabricated tissue constructs with neuromuscular junctions.

Acta Biomater 2021 02 13;121:237-249. Epub 2020 Dec 13.

Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1094, USA. Electronic address:

Damages in pelvic floor muscles often cause dysfunction of the entire pelvic urogenital system, which is clinically challenging. A bioengineered skeletal muscle construct that mimics structural and functional characteristics of native skeletal muscle could provide a therapeutic option to restore normal muscle function. However, most of the current bioengineered muscle constructs are unable to provide timely innervation necessary for successful grafting and functional recovery. Read More

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February 2021

Alternative Splicing and the Intracellular Domain Mediate TM-agrin's Ability to Differentially Regulate the Density of Excitatory and Inhibitory Synapse-like Specializations in Developing CNS Neurons.

Neuroscience 2019 11 28;419:60-71. Epub 2019 Oct 28.

Department of Physiological Genomics, Biomedical Center, Ludwig-Maximilians-University, Großhaderner Str. 9, D-82152 Planegg-Martinsried, Germany. Electronic address:

Agrin is a multi-domain protein best known for its essential function during formation of the neuromuscular junction. Alternative mRNA splicing at sites named y and z in the C-terminal part of agrin regulates its interaction with a receptor complex consisting of the agrin-binding low-density lipoprotein receptor-related protein 4 (Lrp4) and the muscle-specific kinase (MuSK). Isoforms with inserts at both splice sites bind to Lrp4, activate MuSK and are synaptogenic at the neuromuscular junction. Read More

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November 2019

Towards frailty biomarkers: Candidates from genes and pathways regulated in aging and age-related diseases.

Ageing Res Rev 2018 Nov 30;47:214-277. Epub 2018 Jul 30.

Novartis Institutes for Biomedical Research, Musculoskeletal Disease Area, Muscle Research, Cambridge, USA. Electronic address:

Objective: Use of the frailty index to measure an accumulation of deficits has been proven a valuable method for identifying elderly people at risk for increased vulnerability, disease, injury, and mortality. However, complementary molecular frailty biomarkers or ideally biomarker panels have not yet been identified. We conducted a systematic search to identify biomarker candidates for a frailty biomarker panel. Read More

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November 2018

Dietary supplementation with bovine-derived milk fat globule membrane lipids promotes neuromuscular development in growing rats.

Nutr Metab (Lond) 2017 23;14. Epub 2017 Jan 23.

Liggins Institute, The University of Auckland, Private Bag 92019, Auckland, 1142 New Zealand.

Background: The milk fat globule membrane (MFGM) is primarily composed of polar phospho- and sphingolipids, which have established biological effects on neuroplasticity. The present study aimed to investigate the effect of dietary MFGM supplementation on the neuromuscular system during post-natal development.

Methods: Growing rats received dietary supplementation with bovine-derived MFGM mixtures consisting of complex milk lipids (CML), beta serum concentrate (BSC) or a complex milk lipid concentrate (CMLc) (which lacks MFGM proteins) from post-natal day 10 to day 70. Read More

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January 2017

Differential regulation of AChR clustering in the polar and equatorial region of murine muscle spindles.

Eur J Neurosci 2015 Jan 6;41(1):69-78. Epub 2014 Nov 6.

Department of Physiological Genomics, Ludwig-Maximilians-University, Pettenkoferstrasse 12, D-80336, Munich, Germany; Helmholtz Center Munich, Neuherberg, Germany.

Intrafusal fibers of muscle spindles are innervated in the central region by afferent sensory axons and at both polar regions by efferent γ-motoneurons. We previously demonstrated that both neuron-muscle contact sites contain cholinergic synapse-like specialisation, including aggregates of the nicotinic acetylcholine receptor (AChR). In this study we tested the hypothesis that agrin and its receptor complex (consisting of LRP4 and the tyrosine kinase MuSK) are involved in the aggregation of AChRs in muscle spindles, similar to their role at the neuromuscular junction. Read More

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January 2015

A mental retardation gene, motopsin/prss12, modulates cell morphology by interaction with seizure-related gene 6.

Biochem Biophys Res Commun 2013 Jul 11;436(4):638-44. Epub 2013 Jun 11.

Department of Rehabilitation Sciences, Gunma University Graduate School of Health Sciences, 3-39-22 Showa, Maebashi 371-8514, Japan.

A serine protease, motopsin (prss12), plays a significant role in cognitive function and the development of the brain, since the loss of motopsin function causes severe mental retardation in humans and enhances social behavior in mice. Motopsin is activity-dependently secreted from neuronal cells, is captured around the synaptic cleft, and cleaves a proteoglycan, agrin. The multi-domain structure of motopsin, consisting of a signal peptide, a proline-rich domain, a kringle domain, three scavenger receptor cysteine-rich domains, and a protease domain at the C-terminal, suggests the interaction with other molecules through these domains. Read More

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Unfolding dynamics of the mucin SEA domain probed by force spectroscopy suggest that it acts as a cell-protective device.

FEBS J 2013 Mar 21;280(6):1491-501. Epub 2013 Feb 21.

Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden.

MUC1 and other membrane-associated mucins harbor long, up to 1 μm, extended highly glycosylated mucin domains and sea urchin sperm protein, enterokinase and agrin (SEA) domains situated on their extracellular parts. These mucins line luminal tracts and organs, and are anchored to the apical cell membrane by a transmembrane domain. The SEA domain is highly conserved and undergoes a molecular strain-dependent autocatalytic cleavage during folding in the endoplasmic reticulum, a process required for apical plasma membrane expression. Read More

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Structural basis of agrin-LRP4-MuSK signaling.

Genes Dev 2012 Feb;26(3):247-58

Center for Neuroscience, Aging, and Stem Cell Research, Sanford-Burnham Medical Research Institute, La Jolla, California 92037, USA.

Synapses are the fundamental units of neural circuits that enable complex behaviors. The neuromuscular junction (NMJ), a synapse formed between a motoneuron and a muscle fiber, has contributed greatly to understanding of the general principles of synaptogenesis as well as of neuromuscular disorders. NMJ formation requires neural agrin, a motoneuron-derived protein, which interacts with LRP4 (low-density lipoprotein receptor-related protein 4) to activate the receptor tyrosine kinase MuSK (muscle-specific kinase). Read More

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February 2012

Evidence for a role of dystroglycan regulating the membrane architecture of astroglial endfeet.

Eur J Neurosci 2011 Jun 19;33(12):2179-86. Epub 2011 Apr 19.

Department of Neurosurgery, Tübingen Medical School, Tübingen, Germany.

The dystrophin-dystroglycan complex (DDC) is a molecular array of proteins in muscle and brain cells. The central component of the DDC is dystroglycan, which comprises α- and β-subunits. α-Dystroglycan (α-DG) binds to extracellular matrix components such as agrin, whereas β-dystroglycan (β-DG) is a membrane-spanning protein linking α-DG to the cytoskeleton and other intracellular components such as α-syntrophin. Read More

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Muscle-wide secretion of a miniaturized form of neural agrin rescues focal neuromuscular innervation in agrin mutant mice.

Proc Natl Acad Sci U S A 2008 Aug 6;105(32):11406-11. Epub 2008 Aug 6.

Biozentrum and Institute of Physiology, Department of Biomedicine, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.

Agrin and its receptor MuSK are required for the formation of the postsynaptic apparatus at the neuromuscular junction (NMJ). In the current model the local deposition of agrin by the nerve and the resulting local activation of MuSK are responsible for creating and maintaining the postsynaptic apparatus including clusters of acetylcholine receptors (AChRs). Concomitantly, the release of acetylcholine (ACh) and the resulting depolarization disperses those postsynaptic structures that are not apposed by the nerve and thus not stabilized by agrin-MuSK signaling. Read More

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Serase-1B, a new splice variant of polyserase-1/TMPRSS9, activates urokinase-type plasminogen activator and the proteolytic activation is negatively regulated by glycosaminoglycans.

Biochem J 2006 Dec;400(3):551-61

Division of Enzyme Chemistry, Institute for Enzyme Research, University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.

Polyserase-1 (polyserine protease-1)/TMPRSS9 (transmembrane serine protease 9) is a type II transmembrane serine protease (TTSP) that possesses unique three tandem serine protease domains. However, the physiological function of each protease domain remains poorly understood. We discovered a new splice variant of polyserase-1, termed Serase-1B, which contains 34 extra amino acids consisting a SEA module (a domain found in sea urchin sperm protein, enterokinase and agrin) adjacent to the transmembrane domain and the first protease domain with a mucin-like box at the C-terminus. Read More

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December 2006

Transmembrane and secreted MUC1 probes show trafficking-dependent changes in O-glycan core profiles.

Glycobiology 2005 Nov 22;15(11):1111-24. Epub 2005 Jun 22.

Center of Biochemistry Medical Facility, University of Cologne, Joseph-Stelzmann-Str. 52, 50931 Köln, Germany.

The human mucin MUC1 is expressed both as a transmembrane heterodimeric protein complex that recycles via the trans-Golgi network (TGN) and as a secreted isoform. To determine whether differences in cellular trafficking might influence the O-glycosylation profiles on these isoforms, we developed a model system consisting of membrane-bound and secretory-recombinant glycosylation probes. Secretory MUC1-S contains only a truncated repeat domain, whereas in MUC1-M constructs this domain is attached to the native transmembrane and cytoplasmic domains of MUC1 either directly (M0) or via an intermitting nonfunctional (M1) or functional sperm protein-enterokinase-agrin (SEA) module (M2); the SEA module contains a putative proteolytic cleavage site and is associated with proteins receiving extensive O-glycosylation. Read More

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November 2005

Basement membrane assembly, stability and activities observed through a developmental lens.

Matrix Biol 2004 Jan;22(7):521-38

Department of Pathology and Laboratory Medicine, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA.

Basement membranes are cell surface associated extracellular matrices containing laminins, type IV collagens, nidogens, perlecan, agrin, and other macromolecules. Biochemical and ultrastructural studies have suggested that basement membrane assembly and integrity is provided through multiple component interactions consisting of self-polymerizations, inter-component binding, and cell surface adhesions. Mutagenesis in vertebrate embryos and embryoid bodies have led to revisions of this model, providing evidence that laminins are essential for the formation of an initial polymeric scaffold of cell-attached matrix which matures in stability, ligand diversity, and functional complexity as additional matrix components are integrated into the scaffold. Read More

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January 2004

Heparan sulfate proteoglycans in glomerular inflammation.

Kidney Int 2004 Mar;65(3):768-85

Nephrology Research Laboratory, Nijmegen Centre for Molecular Life Sciences, University Medical Centre, Nijmegen, The Netherlands.

Heparan sulfate proteoglycans (HSPGs) are glycoproteins consisting of a core protein to which linear heparan sulfate side chains are covalently attached. These heparan sulfate side chains can be modified at different positions by several enzymes, which include N-deacetylases, N- and O-sulfotransferases, and an epimerase. These heparan sulfate modifications give rise to an enormous structural diversity, which corresponds to the variety of biologic functions mediated by heparan sulfate, including its role in inflammation. Read More

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The adrenal secretory serine protease AsP is a short secretory isoform of the transmembrane airway trypsin-like protease.

Endocrinology 2004 Apr 22;145(4):1898-905. Epub 2003 Dec 22.

Endocrinology and Diabetes Unit, Department of Medicine, University of Wuerzburg, Germany.

To further elucidate the role of proteases capable of cleaving N-terminal proopiomelanocortin (N-POMC)-derived peptides, we have cloned two cDNAs encoding isoforms of the airway trypsin-like protease (AT) from mouse (MAT) and rat (RAT), respectively. The open reading frames comprise 417 amino acids (aa) and 279 aa. The mouse AT gene was located at chromosome 5E1 and contains 10 exons. Read More

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NMR structure of the netrin-like domain (NTR) of human type I procollagen C-proteinase enhancer defines structural consensus of NTR domains and assesses potential proteinase inhibitory activity and ligand binding.

J Biol Chem 2003 Jul 1;278(28):25982-9. Epub 2003 Apr 1.

Department of Medical Biochemistry and Biophysics, Karolinska Institute, S-17177 Stockholm, Sweden.

Procollagen C-proteinase enhancer (PCOLCE) proteins are extracellular matrix proteins that enhance the activities of procollagen C-proteinases by binding to the C-propeptide of procollagen I. PCOLCE proteins are built of three structural modules, consisting of two CUB domains followed by a C-terminal netrin-like (NTR) domain. While the enhancement of proteinase activity can be ascribed solely to the CUB domains, sequence homology of the NTR domain with tissue inhibitors of metalloproteinases suggest proteinase inhibitory activity for the NTR domain. Read More

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Cleavage of Ig-Hepta at a "SEA" module and at a conserved G protein-coupled receptor proteolytic site.

J Biol Chem 2002 Jun 24;277(26):23391-8. Epub 2002 Apr 24.

Department of Biological Sciences, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.

Ig-Hepta is a member of a new subfamily of the heptahelical receptors and has an unusually long N terminus extending toward the extracellular side of the plasma membrane. Pulse-chase experiments in 293T cells using antisera specifically recognizing its N- and C-terminal regions demonstrated that Ig-Hepta is core-glycosylated cotranslationally and proteolytically processed into a two-chain form in the endoplasmic reticulum, followed by maturation of oligosaccharide chains and dimerization. The cleavage occurs at two highly conserved sites: one in a "SEA" module (a module first identified in sperm protein, enterokinase, and agrin) near the N terminus and the other in the stalk region preceding the first transmembrane span, generating approximately 20-, 130-, and 32-kDa fragments. Read More

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