Gene Symbol: Agrn
Description: agrin
Alias: AGR, agrin
Species: rat
Products:     Agrn

Top Publications

  1. 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...
  2. 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...
  3. Groffen A, Ruegg M, Dijkman H, van de Velden T, Buskens C, van den Born J, et al. Agrin is a major heparan sulfate proteoglycan in the human glomerular basement membrane. J Histochem Cytochem. 1998;46:19-27 pubmed
    b>Agrin is a heparan sulfate proteoglycan (HSPG) that is highly concentrated in the synaptic basal lamina at the neuromuscular junction (NMJ). Agrin-like immunoreactivity is also detected outside the NMJ...
  4. Burgess R, Nguyen Q, Son Y, Lichtman J, Sanes J. Alternatively spliced isoforms of nerve- and muscle-derived agrin: their roles at the neuromuscular junction. Neuron. 1999;23:33-44 pubmed
    b>Agrin induces synaptic differentiation at the skeletal neuromuscular junction (NMJ); both pre- and postsynaptic differentiation are drastically impaired in its absence...
  5. Rupp F, Payan D, Magill Solc C, Cowan D, Scheller R. Structure and expression of a rat agrin. Neuron. 1991;6:811-23 pubmed
    b>Agrin is a component of the basal lamina that causes the aggregation of acetylcholine receptors on cultured muscle fibers...
  6. Glass D, Bowen D, Stitt T, Radziejewski C, Bruno J, Ryan T, et al. Agrin acts via a MuSK receptor complex. Cell. 1996;85:513-23 pubmed
    ..b>Agrin is a nerve-derived factor that can induced molecular reorganizations at the motor endplate, but the mechanism of ..
  7. Rupp F, Ozcelik T, Linial M, Peterson K, Francke U, Scheller R. Structure and chromosomal localization of the mammalian agrin gene. J Neurosci. 1992;12:3535-44 pubmed
    b>Agrin, a component of the synaptic basal lamina, has been shown to induce clustering of ACh receptors on the surface of muscle fibers...
  8. Mittaud P, Camilleri A, Willmann R, Erb Vögtli S, Burden S, Fuhrer C. A single pulse of agrin triggers a pathway that acts to cluster acetylcholine receptors. Mol Cell Biol. 2004;24:7841-54 pubmed
    b>Agrin triggers signaling mechanisms of high temporal and spatial specificity to achieve phosphorylation, clustering, and stabilization of postsynaptic acetylcholine receptors (AChRs)...
  9. McCroskery S, Chaudhry A, Lin L, Daniels M. Transmembrane agrin regulates filopodia in rat hippocampal neurons in culture. Mol Cell Neurosci. 2006;33:15-28 pubmed
    ..The transmembrane isoform of the proteoglycan agrin, expressed predominantly in the CNS, may regulate neurite outgrowth, synapse formation and excitatory signaling...

Scientific Experts

More Information


  1. McCroskery S, Bailey A, Lin L, Daniels M. Transmembrane agrin regulates dendritic filopodia and synapse formation in mature hippocampal neuron cultures. Neuroscience. 2009;163:168-79 pubmed publisher
    The transmembrane isoform of agrin (Tm-agrin) is the predominant form expressed in the brain but its putative roles in brain development are not well understood...
  2. Burgess R, Skarnes W, Sanes J. Agrin isoforms with distinct amino termini: differential expression, localization, and function. J Cell Biol. 2000;151:41-52 pubmed
    The proteoglycan agrin is required for postsynaptic differentiation at the skeletal neuromuscular junction, but is also associated with basal laminae in numerous other tissues, and with the surfaces of some neurons...
  3. 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, ..
  4. 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...
  5. Kim N, Stiegler A, Cameron T, Hallock P, Gomez A, Huang J, et al. Lrp4 is a receptor for Agrin and forms a complex with MuSK. Cell. 2008;135:334-42 pubmed publisher
    ..MuSK, a receptor tyrosine kinase that is expressed in skeletal muscle, and Agrin, a motor neuron-derived ligand that stimulates MuSK phosphorylation, play critical roles in synaptic ..
  6. Gautam M, Noakes P, Moscoso L, Rupp F, Scheller R, Merlie J, et al. Defective neuromuscular synaptogenesis in agrin-deficient mutant mice. Cell. 1996;85:525-35 pubmed
    ..The protein agrin, originally isolated from the basal lamina of the synaptic cleft, is synthesized and secreted by motoneurons and ..
  7. Gee S, Montanaro F, Lindenbaum M, Carbonetto S. Dystroglycan-alpha, a dystrophin-associated glycoprotein, is a functional agrin receptor. Cell. 1994;77:675-86 pubmed
    ..of acetylcholine receptors (AChRs) on skeletal muscle fibers is thought to be mediated by the basal lamina protein agrin. Structural similarities shared by agrin and laminin suggested that the laminin receptor dystroglycan-alpha, part ..
  8. Porten E, Seliger B, Schneider V, Wöll S, Stangel D, Ramseger R, et al. The process-inducing activity of transmembrane agrin requires follistatin-like domains. J Biol Chem. 2010;285:3114-25 pubmed publisher
    Clustering or overexpression of the transmembrane form of the extracellular matrix proteoglycan agrin in neurons results in the formation of numerous highly motile filopodia-like processes extending from axons and dendrites...
  9. Zhang B, Luo S, Wang Q, Suzuki T, Xiong W, Mei L. LRP4 serves as a coreceptor of agrin. Neuron. 2008;60:285-97 pubmed publisher
    Neuromuscular junction (NMJ) formation requires agrin, a factor released from motoneurons, and MuSK, a transmembrane tyrosine kinase that is activated by agrin. However, how signal is transduced from agrin to MuSK remains unclear...
  10. 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 ..
  11. Tseng C, Zhang L, Wu S, Wang W, Wang Z, Cascio M. Asparagine of z8 insert is critical for the affinity, conformation, and acetylcholine receptor-clustering activity of neural agrin. J Biol Chem. 2010;285:27641-51 pubmed publisher
    b>Agrin isoforms with different bioactivities are synthesized by the nerve and the muscle...
  12. Samuel M, Valdez G, Tapia J, Lichtman J, Sanes J. Agrin and synaptic laminin are required to maintain adult neuromuscular junctions. PLoS ONE. 2012;7:e46663 pubmed publisher
    ..At the skeletal neuromuscular junction (NMJ), these molecules include agrin, a nerve-derived organizer of postsynaptic differentiation, and synaptic laminins, muscle-derived organizers of ..
  13. Noakes P, Miner J, Gautam M, Cunningham J, Sanes J, Merlie J. The renal glomerulus of mice lacking s-laminin/laminin beta 2: nephrosis despite molecular compensation by laminin beta 1. Nat Genet. 1995;10:400-6 pubmed
    ..Laminin beta 2-deficient mice may provide a model for human congenital or idiopathic nephrotic syndromes...
  14. Chiamulera C, Di Chio M, Tedesco V, Cantù C, Formaggio E, Fumagalli G. Nicotine-induced phosphorylation of phosphorylated cyclic AMP response element-binding protein (pCREB) in hippocampal neurons is potentiated by agrin. Neurosci Lett. 2008;442:234-8 pubmed publisher
    The scope of this study was to test whether increased levels of the extracellular matrix molecule (ECM) agrin might enhance nicotine effects on those molecular mechanisms that initiate neuroadaptative processes in the hippocampus, a key ..
  15. Hilgenberg L, Su H, Gu H, O Dowd D, Smith M. Alpha3Na+/K+-ATPase is a neuronal receptor for agrin. Cell. 2006;125:359-69 pubmed
    b>Agrin, through its interaction with the receptor tyrosine kinase MuSK, mediates accumulation of acetylcholine receptors (AChR) at the developing neuromuscular junction. Agrin has also been implicated in several functions in brain...
  16. Stephan A, Mateos J, Kozlov S, Cinelli P, Kistler A, Hettwer S, et al. Neurotrypsin cleaves agrin locally at the synapse. FASEB J. 2008;22:1861-73 pubmed publisher
    ..Neurotrypsin cleaves agrin at two homologous sites, liberating a 90-kDa and a C-terminal 22-kDa fragment from the N-terminal moiety of agrin...
  17. Kanagawa M, Saito F, Kunz S, Yoshida Moriguchi T, Barresi R, Kobayashi Y, et al. Molecular recognition by LARGE is essential for expression of functional dystroglycan. Cell. 2004;117:953-64 pubmed
    ..Therefore, molecular recognition of dystroglycan by LARGE is a key determinant in the biosynthetic pathway to produce mature and functional dystroglycan. ..
  18. Witzemann V, Chevessier F, Pacifici P, Yampolsky P. The neuromuscular junction: selective remodeling of synaptic regulators at the nerve/muscle interface. Mech Dev. 2013;130:402-11 pubmed publisher
    ..The results show that detailed analysis of mouse models will help to understand the complexity in mechanisms that regulate synaptic remodeling. ..
  19. Bach A, Beier J, Stark G. Expression of Trisk 51, agrin and nicotinic-acetycholine receptor epsilon-subunit during muscle development in a novel three-dimensional muscle-neuronal co-culture system. Cell Tissue Res. 2003;314:263-74 pubmed
    ..Pharmacological tests suggested the formation of neuromuscular junctions. The analysis of neural agrin expression and myogenic desmin, myogenin, MyoD, Trisk 51, and nicotinic-acetycholine receptor (nACh-receptor) ..
  20. Winzen U, Cole G, Halfter W. Agrin is a chimeric proteoglycan with the attachment sites for heparan sulfate/chondroitin sulfate located in two multiple serine-glycine clusters. J Biol Chem. 2003;278:30106-14 pubmed
    b>Agrin is a large extracellular matrix protein that plays a key role in the formation and maintenance of the vertebrate neuromuscular junction...
  21. Baumann E, Preston E, Slinn J, Stanimirovic D. Post-ischemic hypothermia attenuates loss of the vascular basement membrane proteins, agrin and SPARC, and the blood-brain barrier disruption after global cerebral ischemia. Brain Res. 2009;1269:185-97 pubmed publisher
    ..In this study, the expression changes of the BM proteoglycan agrin, and the non-structural BM constituent SPARC (BM-40, osteonectin), were studied in brain vessels after global ..
  22. 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 ..
  23. Lin L, McCroskery S, Ross J, Chak Y, Neuhuber B, Daniels M. Induction of filopodia-like protrusions by transmembrane agrin: role of agrin glycosaminoglycan chains and Rho-family GTPases. Exp Cell Res. 2010;316:2260-77 pubmed publisher
    ..Recent reports suggest that the transmembrane form of the widely expressed proteoglycan agrin (TM-agrin) regulates formation and stability of neuronal filopodia...
  24. 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 ..
  25. Cui J, Bazan N. Agrin downregulation induced by nerve injury contributes to neuropathic pain. J Neurosci. 2010;30:15286-97 pubmed publisher
    ..Here we show that peripheral nerve injury decreased agrin expression in the ipsilateral spinal dorsal horn of rats displaying tactile allodynia...
  26. Zong Y, Zhang B, Gu S, Lee K, Zhou J, Yao G, et al. Structural basis of agrin-LRP4-MuSK signaling. Genes Dev. 2012;26:247-58 pubmed publisher
    ..NMJ formation requires neural agrin, a motoneuron-derived protein, which interacts with LRP4 (low-density lipoprotein receptor-related protein 4) to ..
  27. Boor I, Nagtegaal M, Kamphorst W, van der Valk P, Pronk J, van Horssen J, et al. MLC1 is associated with the dystrophin-glycoprotein complex at astrocytic endfeet. Acta Neuropathol. 2007;114:403-10 pubmed
    ..We demonstrated a direct protein interaction between MLC1 and Kir4.1. From these results we conclude that MLC1 is associated with the DGC at astrocytic endfeet...
  28. Trinidad J, Cohen J. Neuregulin inhibits acetylcholine receptor aggregation in myotubes. J Biol Chem. 2004;279:31622-8 pubmed
    ..of acetylcholine receptors (AChRs) at the vertebrate neuromuscular junction results from their aggregation by the agrin/MuSK signaling pathway and their synthetic up-regulation by the neuregulin/ErbB pathway...
  29. Luo Z, Wang Q, Zhou J, Wang J, Luo Z, Liu M, et al. Regulation of AChR clustering by Dishevelled interacting with MuSK and PAK1. Neuron. 2002;35:489-505 pubmed
    ..Disruption of the MuSK-Dvl interaction inhibits Agrin- and neuron-induced AChR clustering...
  30. Martin A, Alonso G, Guerineau N. [An unexpected role for agrin on cell-to-cell coupling during synaptogenesis]. Med Sci (Paris). 2005;21:913-5 pubmed
  31. Gingras J, Spicer J, Altares M, Zhu Q, Kuchel G, Ferns M. Agrin becomes concentrated at neuroeffector junctions in developing rodent urinary bladder. Cell Tissue Res. 2005;320:115-25 pubmed
    ..of somatic neuromuscular junctions in skeletal muscle is regulated by an extracellular matrix protein called agrin. Here, we have examined the expression and localization of agrin during development of the rodent urinary bladder, ..
  32. 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...
  33. Mis K, Matkovic U, Pirkmajer S, Sciancalepore M, Lorenzon P, Mars T, et al. Acetylcholinesterase and agrin: different functions, similar expression patterns, multiple roles. Chem Biol Interact. 2013;203:297-301 pubmed publisher
    Acetylcholinesterase (AChE) and agrin play unique functional roles in the neuromuscular junction (NMJ). AChE is a cholinergic and agrin a synaptogenetic component...
  34. Martin A, Alonso G, Guerineau N. Agrin mediates a rapid switch from electrical coupling to chemical neurotransmission during synaptogenesis. J Cell Biol. 2005;169:503-14 pubmed
    ..actions as an organizer of synaptic differentiation at the neuromuscular junction, the proteoglycan agrin is still in search of a function in the nervous system...
  35. Bandi E, Jevsek M, Mars T, Jurdana M, Formaggio E, Sciancalepore M, et al. Neural agrin controls maturation of the excitation-contraction coupling mechanism in human myotubes developing in vitro. Am J Physiol Cell Physiol. 2008;294:C66-73 pubmed
    ..conditioned by cocultures, and 4) aneurally cultured in medium supplemented with purified recombinant chick neural agrin. Ca(2+) imaging indicated that coculturing human muscle cells with rat spinal cord explants increased the fraction ..
  36. Bergstrom R, Sinjoanu R, Ferreira A. Agrin induced morphological and structural changes in growth cones of cultured hippocampal neurons. Neuroscience. 2007;149:527-36 pubmed
    The role of agrin in synaptogenesis has been extensively studied. On the other hand, little is known about the function of this extracellular matrix protein during developmental processes that precede the formation of synapses...
  37. Neuhuber B, Daniels M. Targeting of recombinant agrin to axonal growth cones. Mol Cell Neurosci. 2003;24:1180-96 pubmed
    ..The heparan sulfate proteoglycan agrin orchestrates postsynaptic differentiation of the neuromuscular junction and may be involved in synaptic ..
  38. Terrado J, Burgess R, DeChiara T, Yancopoulos G, Sanes J, Kato A. Motoneuron survival is enhanced in the absence of neuromuscular junction formation in embryos. J Neurosci. 2001;21:3144-50 pubmed
    ..e., null mutants for agrin, nerve-derived agrin, rapsyn, and MuSK)...
  39. Gramolini A, Burton E, Tinsley J, Ferns M, Cartaud A, Cartaud J, et al. Muscle and neural isoforms of agrin increase utrophin expression in cultured myotubes via a transcriptional regulatory mechanism. J Biol Chem. 1998;273:736-43 pubmed
    ..J. (1997) J. Biol. Chem. 272, 8117-8120). In the present study, we have therefore focused on the effect of agrin on utrophin expression in cultured C2 myotubes...
  40. Falo M, Reeves T, Phillips L. Agrin expression during synaptogenesis induced by traumatic brain injury. J Neurotrauma. 2008;25:769-83 pubmed publisher
    ..We now report protein and mRNA analysis of agrin, a MMP-3 substrate, over the time course of trauma-induced synaptogenesis...
  41. Zhang W, Coldefy A, Hubbard S, Burden S. Agrin binds to the N-terminal region of Lrp4 protein and stimulates association between Lrp4 and the first immunoglobulin-like domain in muscle-specific kinase (MuSK). J Biol Chem. 2011;286:40624-30 pubmed publisher
    ..Motor axons supply Agrin, which binds Lrp4 and stimulates further MuSK phosphorylation, stabilizing nascent synapses...
  42. Erasso D, Tender G, Levitt R, Cui J. Agrin requires specific proteins to selectively activate γ-aminobutyric acid neurons for pain suppression. Exp Neurol. 2014;261:646-53 pubmed publisher
    b>Agrin, a heparan sulfate proteoglycan functioning as a neuro-muscular junction inducer, has been shown to inhibit neuropathic pain in sciatic nerve injury rat models, via phosphorylation of N-Methyl-d-aspartate receptor NR1 subunits in ..