Agrin

A neurally derived signaling protein, agrin, acts through a receptor tyrosine kinase, MuSK, in the formation of the specialized postsynaptic endplate by interaction with rapsyn. Thus, MuSK-rapsyn interactions are critical in forming the local scaffold for postsynaptic components in the motor endplate [43,44]. 

The putative receptor for agrin is a RPTK known as muscle-specific kinase (MuSK). The extracellular domain of MuSK resembles that of the ROR family of RPTKs, while the kinase domain is similar to that of the Trk neurotrophic receptor (Fig. 24-6). MuSK is expressed at low concentrations in proliferating myoblasts and is induced... 

McMahan, U. J. The agrin hypothesis. Cold Spring Harbor Symp. Quant. Biol. 55 407-418,1990. 

Gautam, M., Noakes, P. G., Moscoso, L. et al. Defective neuromuscular synaptogenesis in agrin-deficient mutant mice. Cell 85 525-535,1996. 

Meyer, G. and Wallace, B. G. Recruitment of a nicotinic acetylcholine receptor mutant lacking cytoplasmic tyrosine residues in its beta subunit into agrin-induced aggregates. Mol. Cell. Neurosci. 11 324-333,1998. 

SEA Domain found in sea urchin sperm protein, enterokinase, agrin E(M) 0(0) 4(6) ... 

LamG (Jelly Sialidases Human agrin laminin G PSI-BLAST (1) 6 X 106 Streptomyces coelicolor sialidase... 

Fig. 20.8. Neuromuscular junctions analyzed by transmission electron microscopy. (A) In wild-type mice, the motor nerve terminal (MN) is depressed into the muscle fiber surface. The terminal is polarized, with small clear vesicles near the presynaptic membrane and mitochondria in the more proximal portion of the terminal. The postsynaptic membrane has deep convolutions (junctional folds, JF) and the membrane near the tops of these folds is very electron dense because of the high density of acetylcholine receptors (arrowheads). (B) In some myasthenias where the nerve sprouts but remains in contact with the muscle, terminals with mitochondria and vesicles are observed in the absence of any postsynaptic specialization. Presumably these are sprouting terminals that have not established a functional connection. (C) Partial innervation of postsynaptic sites is evident as elaborate junctional folds in the muscle membrane with no overlying nerve terminal. In these examples, the interpretations were aided by light microscopy examination of other samples as described in Fig. 20.8 in parallel with electron microscopy. The mutation shown in (B, C) is an unpublished ENU-induced allele of agrin.

Burgess, R. W., Skarnes, W. C. and Sanes, J. R. (2000) Agrin isoforms with distinct amino... 

Harvey, S. J., Jarad, G., Cunningham, J., Rops, A. L., van der Vlag, J., Berden, J. H., et al. (2007) Disruption of glomerular basement membrane charge through podocyte-specific mutation of agrin does not alter glomerular permselectivity. Am J Pathol 171, 139-152. 

Wolfram T, Spatz JP, Burgess RW (2008) 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 9 64... 

Hohenester, E., Tisi, D., Talts, J. F., and Timpl, R. (1999). The crystal structure of a laminin G-like module reveals the molecular basis of a-dystroglycan binding to laminins, perlecan, and agrin. Mol. Cell 4, 783-792. 

Mars, T., King, M.P., Miranda, A.F., Walker, W.F., Mis, K., Gmbic, Z. (2003). Functional innervation of cultured human skeletal muscle proceeds by two modes with regard to agrin effects. Neuroscience 118 87-97. 

Stetzkowski-Marden F, Gaus K, Recouvreur M, Cartaud A, Cartaud J (2006) Agrin elicits membrane lipid condensation at sites of acetylcholine receptor clusters in C2C12 myotubes. J Lipid Res 47 2121-2133... 

Luck G, Hoch W, Hopf C, Blottner D. 2000. Nitric oxide synthase (NOS-1) coclustered with agrin-induced AChR-specializations on cultured skeletal myotubes. Mol Cell Neurosci 16 268-281. 

Heparin is synthesized in connective-tissue type mast cells, as part of the serglycin proteoglycan. HS is produced by most mammalian (and many other) cells and is bound to a variety of core proteins, in particular syndecans, gly-picans, perlecan, and agrin. Following translation in the rough endoplasmic... 

Syndecan and glypican are both cell memhrane-associated proteoglycans, while perlecan, agrin, and type XVIII collagen are extracellular components (Figure 2). Syndecan contains an integral membrane protein and... 

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