agrin

Summary

Summary: A protein component of the synaptic basal lamina. It has been shown to induce clustering of acetylcholine receptors on the surface of muscle fibers and other synaptic molecules in both synapse regeneration and development.

Top Publications

  1. Inoue A, Setoguchi K, Matsubara Y, Okada K, Sato N, Iwakura Y, et al. Dok-7 activates the muscle receptor kinase MuSK and shapes synapse formation. Sci Signal. 2009;2:ra7 pubmed publisher
    ..neuromuscular junction (NMJ) is orchestrated by the muscle-specific receptor tyrosine kinase MuSK and by neural agrin, an extracellular activator of MuSK...
  2. Wolburg H, Noell S, Wolburg Buchholz K, Mack A, Fallier Becker P. Agrin, aquaporin-4, and astrocyte polarity as an important feature of the blood-brain barrier. Neuroscientist. 2009;15:180-93 pubmed publisher
  3. Hilgenberg L, Pham B, Ortega M, Walid S, Kemmerly T, O Dowd D, et al. Agrin regulation of alpha3 sodium-potassium ATPase activity modulates cardiac myocyte contraction. J Biol Chem. 2009;284:16956-65 pubmed publisher
    ..We recently demonstrated that agrin, a protein first identified at the vertebrate neuromuscular junction, binds to and regulates the activity of ..
  4. Noell S, Wolburg Buchholz K, Mack A, Ritz R, Tatagiba M, Beschorner R, et al. Dynamics of expression patterns of AQP4, dystroglycan, agrin and matrix metalloproteinases in human glioblastoma. Cell Tissue Res. 2012;347:429-41 pubmed publisher
    ..Recently, we were able to show that the extracellular matrix component agrin is important for the construction and localization of the so-called orthogonal arrays of particles (OAPs), which ..
  5. Hrus A, Lau G, Hutter H, Schenk S, Ferralli J, Brown Luedi M, et al. C. elegans agrin is expressed in pharynx, IL1 neurons and distal tip cells and does not genetically interact with genes involved in synaptogenesis or muscle function. PLoS ONE. 2007;2:e731 pubmed
    b>Agrin is a basement membrane protein crucial for development and maintenance of the neuromuscular junction in vertebrates. The C. elegans genome harbors a putative agrin gene agr-1...
  6. Smith M, Hilgenberg L. Agrin in the CNS: a protein in search of a function?. Neuroreport. 2002;13:1485-95 pubmed
    The extracellular matrix molecule agrin mediates the motor neuron induced accumulation of acetylcholine receptors (AChR) at the neuromuscular junction. Agrin is also present in the CNS...
  7. Borges L, Ferns M. Agrin-induced phosphorylation of the acetylcholine receptor regulates cytoskeletal anchoring and clustering. J Cell Biol. 2001;153:1-12 pubmed
    At the developing neuromuscular junction, a motoneuron-derived factor called agrin signals through the muscle-specific kinase receptor to induce postsynaptic aggregation of the acetylcholine receptor (AChR)...
  8. Banyai L, Sonderegger P, Patthy L. Agrin binds BMP2, BMP4 and TGFbeta1. PLoS ONE. 2010;5:e10758 pubmed publisher
    ..vertebrate agrins is sufficient to induce clustering of acetylcholine receptors but despite two decades of intense agrin research very little is known about the function of the other isoforms and the function of the larger, N-terminal ..
  9. Verbeek M, Otte Holler I, van den Born J, van den Heuvel L, David G, Wesseling P, et al. Agrin is a major heparan sulfate proteoglycan accumulating in Alzheimer's disease brain. Am J Pathol. 1999;155:2115-25 pubmed
    ..We performed a comparative immunohistochemical analysis of the expression of the HSPGs agrin, perlecan, glypican-1, and syndecans 1-3 in the lesions of DAT brain neocortex and hippocampus...

More Information

Publications62

  1. Bezakova G, Helm J, Francolini M, Lømo T. Effects of purified recombinant neural and muscle agrin on skeletal muscle fibers in vivo. J Cell Biol. 2001;153:1441-52 pubmed
    Aggregation of acetylcholine receptors (AChRs) in muscle fibers by nerve-derived agrin plays a key role in the formation of neuromuscular junctions...
  2. Mascarenhas J, Ruegg M, Winzen U, Halfter W, Engel J, Stetefeld J. Mapping of the laminin-binding site of the N-terminal agrin domain (NtA). EMBO J. 2003;22:529-36 pubmed
    b>Agrin is a key organizer of acetylcholine receptor (AChR) clustering at the neuromuscular junction. The binding of agrin to laminin is required for its localization to synaptic basal lamina and other basement membranes...
  3. Bogdanik L, Burgess R. A valid mouse model of AGRIN-associated congenital myasthenic syndrome. Hum Mol Genet. 2011;20:4617-33 pubmed publisher
    ..Mutations in AGRIN (AGRN) and other genes in the AGRIN signaling pathway cause CMS, and gene targeting studies in mice confirm the ..
  4. Wolfram T, Spatz J, Burgess R. Cell adhesion to agrin presented as a nanopatterned substrate is consistent with an interaction with the extracellular matrix and not transmembrane adhesion molecules. BMC Cell Biol. 2008;9:64 pubmed publisher
    ..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...
  5. Matsumoto Miyai K, Sokolowska E, Zurlinden A, Gee C, Lüscher D, Hettwer S, et al. Coincident pre- and postsynaptic activation induces dendritic filopodia via neurotrypsin-dependent agrin cleavage. Cell. 2009;136:1161-71 pubmed publisher
    ..the activity-dependent release of neurotrypsin from presynaptic terminals and proteolytical cleavage of agrin at the synapse...
  6. Sole S, Petegnief V, Gorina R, Chamorro A, Planas A. Activation of matrix metalloproteinase-3 and agrin cleavage in cerebral ischemia/reperfusion. J Neuropathol Exp Neurol. 2004;63:338-49 pubmed
    ..Here we examine the expression, activation, and cellular location of MMP-3 and the cleavage of agrin, an MMP-3 substrate, following transient middle cerebral artery occlusion in the rat...
  7. Bentzinger C, Barzaghi P, Lin S, Ruegg M. Overexpression of mini-agrin in skeletal muscle increases muscle integrity and regenerative capacity in laminin-alpha2-deficient mice. FASEB J. 2005;19:934-42 pubmed
    ..We have recently shown that overexpression of a miniaturized form of the molecule agrin (mini-agrin) counteracts the disease in dy(W)/dy(W) mice, a model for MDC1A...
  8. Witzemann V. Development of the neuromuscular junction. Cell Tissue Res. 2006;326:263-71 pubmed
    ..A further neuronal factor, agrin, stabilizes the accumulation of AChR at synaptic sites...
  9. Cotman S, Halfter W, Cole G. Agrin binds to beta-amyloid (Abeta), accelerates abeta fibril formation, and is localized to Abeta deposits in Alzheimer's disease brain. Mol Cell Neurosci. 2000;15:183-98 pubmed
    b>Agrin is an extracellular matrix heparan sulfate proteoglycan (HSPG) well known for its role in modulation of the neuromuscular junction during development...
  10. Joosten S, Sijpkens Y, van Ham V, Trouw L, van der Vlag J, van den Heuvel B, et al. Antibody response against the glomerular basement membrane protein agrin in patients with transplant glomerulopathy. Am J Transplant. 2005;5:383-93 pubmed
    ..with patient IgG showed a GBM-like staining pattern and colocalization with the HSPGs perlecan and especially agrin. Using patient IgG, we affinity purified the antigen and identified it as agrin...
  11. Han H, Noakes P, Phillips W. Overexpression of rapsyn inhibits agrin-induced acetylcholine receptor clustering in muscle cells. J Neurocytol. 1999;28:763-75 pubmed
    ..KORAP myotubes displayed no AChR aggregates before or after treatment with neural agrin. After transfection with rapsyn expression plasmid, some KORAP myotubes expressed rapsyn at physiological levels...
  12. McDonnell K, Grow W. Reduced glycosaminoglycan sulfation diminishes the agrin signal transduction pathway. Dev Neurosci. 2004;26:1-10 pubmed
    ..Chlorate treatment is shown here to decrease the frequency of agrin-induced AChR clustering and agrin-induced tyrosine phosphorylation of the AChR beta-subunit...
  13. Bruneau E, Macpherson P, Goldman D, Hume R, Akaaboune M. The effect of agrin and laminin on acetylcholine receptor dynamics in vitro. Dev Biol. 2005;288:248-58 pubmed
    ..clusters on cultured myotubes in the absence or presence of the nerve-derived clustering factor, agrin. Using fluorescence recovery after photobleaching (FRAP) on fluorescent bungarotoxin-labeled receptors, we found ..
  14. Husain N, Pellikka M, Hong H, Klimentova T, Choe K, Clandinin T, et al. The agrin/perlecan-related protein eyes shut is essential for epithelial lumen formation in the Drosophila retina. Dev Cell. 2006;11:483-93 pubmed
    ..Eys is closely related to the proteoglycans agrin and perlecan and secreted by photoreceptor cells into the interrhabdomeral space...
  15. Zhu D, Xiong W, Mei L. Lipid rafts serve as a signaling platform for nicotinic acetylcholine receptor clustering. J Neurosci. 2006;26:4841-51 pubmed
    b>Agrin, a motoneuron-derived factor, and the muscle-specific receptor tyrosine kinase (MuSK) are essential for the acetylcholine receptor (AChR) clustering at the postjunctional membrane...
  16. Tseng C, Zhang L, Cascio M, Wang Z. Calcium plays a critical role in determining the acetylcholine receptor-clustering activities of alternatively spliced isoforms of Agrin. J Biol Chem. 2003;278:17236-45 pubmed
    Neural agrin, an extracellular matrix protein secreted by motor neurons, plays a key role in clustering of nicotinic acetylcholine receptors (AChR) on postsynaptic membranes of the neuromuscular junction...
  17. Hilgenberg L, Ho K, Lee D, O Dowd D, Smith M. Agrin regulates neuronal responses to excitatory neurotransmitters in vitro and in vivo. Mol Cell Neurosci. 2002;19:97-110 pubmed
    b>Agrin mediates motor neuron-induced differentiation of the postsynaptic apparatus of the neuromuscular junction but its function in brain remains unknown...
  18. Lee C, Han J, Bamburg J, Han L, Lynn R, Zheng J. Regulation of acetylcholine receptor clustering by ADF/cofilin-directed vesicular trafficking. Nat Neurosci. 2009;12:848-56 pubmed publisher
    ..These results suggest that spatiotemporally restricted ADF/cofilin-mediated actin dynamics regulate AChR trafficking during the development of neuromuscular synapses. ..
  19. Kroger S, Schröder J. Agrin in the developing CNS: new roles for a synapse organizer. News Physiol Sci. 2002;17:207-12 pubmed
    The heparan sulfate proteoglycan agrin is responsible for the formation, maintenance, and regeneration of the neuromuscular junction...
  20. Bezakova G, Ruegg M. New insights into the roles of agrin. Nat Rev Mol Cell Biol. 2003;4:295-308 pubmed
    The heparan sulphate proteoglycan agrin is expressed as several isoforms in various tissues...
  21. Eusebio A, Oliveri F, Barzaghi P, Ruegg M. Expression of mouse agrin in normal, denervated and dystrophic muscle. Neuromuscul Disord. 2003;13:408-15 pubmed
    b>Agrin is a heparan sulfate proteoglycan that is required for the development of postsynaptic specializations at the neuromuscular junction...
  22. Li Z, Hilgenberg L, O Dowd D, Smith M. Formation of functional synaptic connections between cultured cortical neurons from agrin-deficient mice. J Neurobiol. 1999;39:547-57 pubmed
    Numerous studies suggest that the extracellular matrix protein agrin directs the formation of the postsynaptic apparatus at the neuromuscular junction (NMJ)...
  23. Zhou H, Glass D, Yancopoulos G, Sanes J. Distinct domains of MuSK mediate its abilities to induce and to associate with postsynaptic specializations. J Cell Biol. 1999;146:1133-46 pubmed
    b>Agrin released from motor nerve terminals activates a muscle-specific receptor tyrosine kinase (MuSK) in muscle cells to trigger formation of the skeletal neuromuscular junction...
  24. Hoch W. Formation of the neuromuscular junction. Agrin and its unusual receptors. Eur J Biochem. 1999;265:1-10 pubmed
    ..between nerve and muscle is initiated by the binding of neurone-specific isoforms of the basal membrane protein agrin to receptors on the surface of myotubes...
  25. Khan A, Bose C, Yam L, Soloski M, Rupp F. Physiological regulation of the immunological synapse by agrin. Science. 2001;292:1681-6 pubmed
    ..We now demonstrate that agrin, an aggregating protein crucial for formation of the neuromuscular junction, is also expressed in lymphocytes and ..
  26. Ferreira A. Abnormal synapse formation in agrin-depleted hippocampal neurons. J Cell Sci. 1999;112 ( Pt 24):4729-38 pubmed
    b>Agrin, a 200 kDa extracellular matrix protein, participates in the maturation of the postsynaptic target at the neuromuscular junction...
  27. Bütikofer L, Zurlinden A, Bolliger M, Kunz B, Sonderegger P. Destabilization of the neuromuscular junction by proteolytic cleavage of agrin results in precocious sarcopenia. FASEB J. 2011;25:4378-93 pubmed publisher
    ..These results suggested the destabilization of the NMJ through proteolytic cleavage of agrin at the onset of a pathogenic pathway ending in sarcopenia...
  28. Luo Z, Je H, Wang Q, Yang F, Dobbins G, Yang Z, et al. Implication of geranylgeranyltransferase I in synapse formation. Neuron. 2003;40:703-17 pubmed
    b>Agrin activates the transmembrane tyrosine kinase MuSK to mediate acetylcholine receptor (AChR) clustering at the neuromuscular junction (NMJ). However, the intracellular signaling mechanism downstream of MuSK is poorly characterized...
  29. Kim N, Burden S. MuSK controls where motor axons grow and form synapses. Nat Neurosci. 2008;11:19-27 pubmed
    ..In addition, ectopic Musk expression stimulates synapse formation in the absence of Agrin and rescues the lethality of Agrn mutant mice, demonstrating that the postsynaptic cell, and MuSK in particular, ..
  30. Chen F, Qian L, Yang Z, Huang Y, Ngo S, Ruan N, et al. Rapsyn interaction with calpain stabilizes AChR clusters at the neuromuscular junction. Neuron. 2007;55:247-60 pubmed
    b>Agrin induces, whereas acetylcholine (ACh) disperses, ACh receptor (AChR) clusters during neuromuscular synaptogenesis...
  31. Camilleri A, Willmann R, Sadasivam G, Lin S, Ruegg M, Gesemann M, et al. Tyrosine phosphatases such as SHP-2 act in a balance with Src-family kinases in stabilization of postsynaptic clusters of acetylcholine receptors. BMC Neurosci. 2007;8:46 pubmed
    ..At the neuromuscular junction (NMJ), agrin/MuSK signaling, by triggering downstream pathways, causes clustering and phosphorylation of postsynaptic ..
  32. Tátrai P, Dudas J, Batmunkh E, Máthé M, Zalatnai A, Schaff Z, et al. Agrin, a novel basement membrane component in human and rat liver, accumulates in cirrhosis and hepatocellular carcinoma. Lab Invest. 2006;86:1149-60 pubmed
    b>Agrin is a multifunctional heparan sulfate proteoglycan originally discovered in the neuromuscular junctions and later observed in numerous other localizations...
  33. Denzer A, Brandenberger R, Gesemann M, Chiquet M, Ruegg M. Agrin binds to the nerve-muscle basal lamina via laminin. J Cell Biol. 1997;137:671-83 pubmed
    b>Agrin is a heparan sulfate proteoglycan that is required for the formation and maintenance of neuromuscular junctions...
  34. Jacobson C, Côté P, Rossi S, Rotundo R, Carbonetto S. The dystroglycan complex is necessary for stabilization of acetylcholine receptor clusters at neuromuscular junctions and formation of the synaptic basement membrane. J Cell Biol. 2001;152:435-50 pubmed
    ..We show that myotubes differentiated from dystroglycan-/- embryonic stem cells are responsive to agrin, but produce acetylcholine receptor (AChR) clusters which are two to three times larger in area, about half as ..
  35. O Toole J, Deyst K, Bowe M, Nastuk M, McKechnie B, Fallon J. Alternative splicing of agrin regulates its binding to heparin alpha-dystroglycan, and the cell surface. Proc Natl Acad Sci U S A. 1996;93:7369-74 pubmed
    b>Agrin is a basal lamina molecule that directs key events in postsynaptic differentiation, most notably the aggregation of acetylcholine receptors (AChRs) on the muscle cell surface...
  36. Yang X, Arber S, William C, Li L, Tanabe Y, Jessell T, et al. Patterning of muscle acetylcholine receptor gene expression in the absence of motor innervation. Neuron. 2001;30:399-410 pubmed
    ..Neurally derived Agrin is dispensable for this early phase of AChR expression, but MuSK, a receptor tyrosine kinase activated by Agrin, ..
  37. Lee L, Kunkel D, Stollberg J. Mechanistic distinctions between agrin and laminin-1 induced aggregation of acetylcholine receptors. BMC Neurosci. 2002;3:10 pubmed
    ..This study presents quantitative analyses of receptor and alpha-Dystroglycan aggregation in response to agrin and laminin-1, alone or in combination...
  38. Borges L, Yechikhov S, Lee Y, Rudell J, Friese M, Burden S, et al. Identification of a motif in the acetylcholine receptor beta subunit whose phosphorylation regulates rapsyn association and postsynaptic receptor localization. J Neurosci. 2008;28:11468-76 pubmed publisher
    ..Here, we define a phosphorylation-dependent binding site on the receptor that mediates agrin-induced clustering...
  39. Gesemann M, Brancaccio A, Schumacher B, Ruegg M. Agrin is a high-affinity binding protein of dystroglycan in non-muscle tissue. J Biol Chem. 1998;273:600-5 pubmed
    b>Agrin is a basement membrane-associated proteoglycan that induces the formation of postsynaptic specializations at the neuromuscular junction...
  40. Mittaud P, Marangi P, Erb Vögtli S, Fuhrer C. Agrin-induced activation of acetylcholine receptor-bound Src family kinases requires Rapsyn and correlates with acetylcholine receptor clustering. J Biol Chem. 2001;276:14505-13 pubmed
    During neuromuscular synaptogenesis, neurally released agrin induces aggregation and tyrosine phosphorylation of acetylcholine receptors (AChRs) by acting through both the receptor tyrosine kinase MuSK (muscle-specific kinase) and the ..
  41. Huh K, Fuhrer C. Clustering of nicotinic acetylcholine receptors: from the neuromuscular junction to interneuronal synapses. Mol Neurobiol. 2002;25:79-112 pubmed
    ..receptors (AChR) is one of the first signs of postsynaptic specialization and is induced by nerve-released agrin. Recent studies have revealed that different mechanisms regulate assembly vs stabilization of AChR clusters and of ..
  42. Cornish T, Branch D, Wheeler B, Campanelli J. Microcontact printing: a versatile technique for the study of synaptogenic molecules. Mol Cell Neurosci. 2002;20:140-53 pubmed
    ..For example, agrin derived from motoneurons induces localized postsynaptic differentiation at the neuromuscular synapse...
  43. Okada K, Inoue A, Okada M, Murata Y, Kakuta S, Jigami T, et al. The muscle protein Dok-7 is essential for neuromuscular synaptogenesis. Science. 2006;312:1802-5 pubmed publisher
    ..Upon innervation, neural agrin activates MuSK to establish the postsynaptic apparatus, although agrin-independent formation of neuromuscular ..
  44. Megeath L, Kirber M, Hopf C, Hoch W, Fallon J. Calcium-dependent maintenance of agrin-induced postsynaptic specializations. Neuroscience. 2003;122:659-68 pubmed
    ..The formation of agrin-induced AChR clusters on cultured myotubes requires both activation of the receptor tyrosine kinase MuSK and ..
  45. Sadasivam G, Willmann R, Lin S, Erb Vögtli S, Kong X, Ruegg M, et al. Src-family kinases stabilize the neuromuscular synapse in vivo via protein interactions, phosphorylation, and cytoskeletal linkage of acetylcholine receptors. J Neurosci. 2005;25:10479-93 pubmed
    ..Rapsyn and the utrophin-glycoprotein complex were recruited normally into AChR-containing clusters by agrin in src(-/-);fyn(-/-) myotubes...
  46. Tournell C, Bergstrom R, Ferreira A. Progesterone-induced agrin expression in astrocytes modulates glia-neuron interactions leading to synapse formation. Neuroscience. 2006;141:1327-38 pubmed
    ..A significant increase in agrin expression was detected in astrocytes cultured in N2 serum-free medium when compared with the ones cultured in ..
  47. Noell S, Fallier Becker P, Beyer C, Kroger S, Mack A, Wolburg H. Effects of agrin on the expression and distribution of the water channel protein aquaporin-4 and volume regulation in cultured astrocytes. Eur J Neurosci. 2007;26:2109-18 pubmed
    b>Agrin is a heparan sulfate proteoglycan of the extracellular matrix and is known for organizing the postsynaptic differentiation of the neuromuscular junction...
  48. Levi S, Grady R, Henry M, Campbell K, Sanes J, Craig A. Dystroglycan is selectively associated with inhibitory GABAergic synapses but is dispensable for their differentiation. J Neurosci. 2002;22:4274-85 pubmed
    ..in synaptogenesis of the major transmembrane component of the DGC, dystroglycan; one of its extracellular ligands, agrin; and one of its cytoskeletal binding partners, dystrophin...
  49. Moransard M, Borges L, Willmann R, Marangi P, Brenner H, Ferns M, et al. Agrin regulates rapsyn interaction with surface acetylcholine receptors, and this underlies cytoskeletal anchoring and clustering. J Biol Chem. 2003;278:7350-9 pubmed
    ..We have investigated whether agrin, a key nerve-derived synaptogenic factor, influences rapsyn-AChR interactions and how this affects clustering and ..
  50. Bixby J, Baerwald de la Torre K, Wang C, Rathjen F, Ruegg M. A neuronal inhibitory domain in the N-terminal half of agrin. J Neurobiol. 2002;50:164-79 pubmed
    b>Agrin is required for appropriate pre- and postsynaptic differentiation of neuromuscular junctions...
  51. Hoover C, Hilgenberg L, Smith M. The COOH-terminal domain of agrin signals via a synaptic receptor in central nervous system neurons. J Cell Biol. 2003;161:923-32 pubmed
    b>Agrin is a motor neuron-derived factor that directs formation of the postsynaptic apparatus of the neuromuscular junction...
  52. Mohamed A, Rivas Plata K, Kraas J, Saleh S, Swope S. Src-class kinases act within the agrin/MuSK pathway to regulate acetylcholine receptor phosphorylation, cytoskeletal anchoring, and clustering. J Neurosci. 2001;21:3806-18 pubmed
    Synaptogenesis at the neuromuscular junction requires agrin-induced stable localization of acetylcholine receptors (AChRs) at the endplate. The effects of agrin are transduced by the muscle-specific receptor tyrosine kinase (MuSK)...
  53. Reif R, Sales S, Hettwer S, Dreier B, Gisler C, Wölfel J, et al. Specific cleavage of agrin by neurotrypsin, a synaptic protease linked to mental retardation. FASEB J. 2007;21:3468-78 pubmed
    ..In the present study, 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 ..