title: 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.
abstract: 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. We have cloned the corresponding cDNA to determine the primary structure of the protein and expressed its recombinant fragments to raise specific antibodies. The domain organization of AGR-1 is very similar to the vertebrate orthologues. C. elegans agrin contains a signal sequence for secretion, seven follistatin domains, three EGF-like repeats and two laminin G domains. AGR-1 loss of function mutants did not exhibit any overt phenotypes and did not acquire resistance to the acetylcholine receptor agonist levamisole. Furthermore, crossing them with various mutants for components of the dystrophin-glycoprotein complex with impaired muscle function did not lead to an aggravation of the phenotypes. Promoter-GFP translational fusion as well as immunostaining of worms revealed expression of agrin in buccal epithelium and the protein deposition in the basal lamina of the pharynx. Furthermore, dorsal and ventral IL1 head neurons and distal tip cells of the gonad arms are sources of agrin production, but no expression was detectable in body muscles or in the motoneurons innervating them. Recombinant worm AGR-1 fragment is able to cluster vertebrate dystroglycan in cultured cells, implying a conservation of this interaction, but since neither of these proteins is expressed in muscle of C. elegans, this interaction may be required in different tissues. The connections between muscle cells and the basement membrane, as well as neuromuscular junctions, are structurally distinct between vertebrates and nematodes.
authors: Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Basel, Switzerland.
authors: Ana
authors: A
authors: Hrus
authors: Gordon
authors: G
authors: Lau
authors: Harald
authors: H
authors: Hutter
authors: Susanne
authors: S
authors: Schenk
authors: Jacqueline
authors: J
authors: Ferralli
authors: Marianne
authors: M
authors: Brown-Luedi
authors: Ruth
authors: R
authors: Chiquet-Ehrismann
authors: Stefano
authors: S
authors: Canevascini
mesh_terms: D018171:Agrin / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002645:Chickens; D049030:Dystroglycans / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D008969:Molecular Sequence Data; D009132:Muscles / Q000166:cytology / Q000502:physiology*; D009469:Neuromuscular Junction / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D014018:Tissue Distribution
chemical_list: D018171:Agrin; D029742:Caenorhabditis elegans Proteins; D011993:Recombinant Fusion Proteins; D049030:Dystroglycans
references: J Cell Biol. 1994 Feb;124(4):475-90
references: 8106547
references: Mol Cell Neurosci. 1992 Oct;3(5):406-17
references: 19912884
references: J Cell Biol. 1997 May 5;137(3):671-83
references: 9151673
references: J Biol Chem. 2006 Dec 1;281(48):36835-45
references: 17012237
references: Nat Neurosci. 2001 Oct;4(10):997-1005
references: 11559854
references: Nature. 1970 Aug 15;227(5259):680-5
references: 5432063
references: Philos Trans R Soc Lond B Biol Sci. 1976 Aug 10;275(938):299-325
references: 8805
references: Neuron. 1991 May;6(5):811-23
references: 1851019
references: J Neurosci. 2003 May 1;23(9):3577-87
references: 12736328
references: Neurogenetics. 1999 Apr;2(2):87-90
references: 10369883
references: J Biol Chem. 2003 May 2;278(18):15457-60
references: 12556455
references: Eur J Biochem. 1998 May 15;254(1):123-8
references: 9652404
references: J Neurosci. 1999 Jan 1;19(1):159-67
references: 9870947
references: Mol Biol Cell. 2000 Nov;11(11):3911-23
references: 11071916
references: Nature. 1995 Nov 2;378(6552):82-5
references: 7477294
references: J Cell Biol. 1987 Dec;105(6 Pt 1):2471-8
references: 2826489
references: Biophys J. 2002 Jan;82(1 Pt 1):493-508
references: 11751336
references: J Cell Biol. 1995 Feb;128(4):625-36
references: 7860635
references: Neurogenetics. 1998 Dec;2(1):61-72
references: 9933302
references: Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7431-5
references: 8395047
references: Curr Opin Neurobiol. 2003 Feb;13(1):70-8
references: 12593984
references: Genetics. 1974 May;77(1):71-94
references: 4366476
references: Genetics. 1995 Jan;139(1):159-69
references: 7535716
references: Mol Cell Neurosci. 2001 Jan;17(1):208-25
references: 11161480
references: Trends Neurosci. 1998 Jan;21(1):22-7
references: 9464682
references: Dev Biol. 1985 Sep;111(1):158-70
references: 3928418
references: J Cell Biol. 1991 Aug;114(3):465-79
references: 1860880
references: Glycobiology. 2003 Aug;13(8):55R-66R
references: 12736199
references: Genes Dev. 1993 Aug;7(8):1471-84
references: 8393416
references: Neuron. 1993 Sep;11(3):479-90
references: 8398141
references: Development. 1999 Dec;126(23):5387-98
references: 10556063
references: EMBO J. 1999 Dec 1;18(23):6762-70
references: 10581249
references: Science. 2001 Jun 1;292(5522):1681-6
references: 11349136
references: Neuron. 1992 Apr;8(4):691-9
references: 1314621
references: J Mol Biol. 2004 Jul 16;340(4):783-95
references: 15223320
references: Philos Trans R Soc Lond B Biol Sci. 1986 Nov 12;314(1165):1-340
references: 22462104
references: Neuron. 1996 Apr;16(4):755-67
references: 8607994
references: J Cell Biol. 2001 Jun 25;153(7):1453-63
references: 11425875
references: Curr Opin Genet Dev. 2002 Jun;12(3):349-61
references: 12076680
references: Neuron. 2005 May 19;46(4):581-94
references: 15944127
references: EMBO J. 1991 Dec;10(12):3959-70
references: 1935914
references: J Cell Biol. 1988 Nov;107(5):1825-33
references: 2846587
references: Science. 1992 Apr 10;256(5054):240-3
references: 1314423
references: FASEB J. 2006 Jan;20(1):50-8
references: 16394267
references: J Exp Biol. 2003 Jul;206(Pt 14):2441-57
references: 12796460
references: J Cell Biol. 1995 Dec;131(6 Pt 1):1547-60
references: 8522611
references: Dev Biol. 2003 Nov 1;263(1):81-102
references: 14568548
references: Genes Dev. 2006 Jul 1;20(13):1800-16
references: 16818610
references: EMBO J. 1988 Oct;7(10):2977-82
references: 2460335
references: Trends Genet. 2000 Jun;16(6):276-7
references: 10827456
references: J Neurosci. 1997 Aug 1;17(15):5843-57
references: 9221782
references: WormBook. 2005;:1-19
references: 18050401
references: Nat Rev Genet. 2002 May;3(5):356-69
references: 11988761
references: WormBook. 2005;:1-15
references: 18050423
references: Exp Gerontol. 2006 Mar;41(3):252-60
references: 16446070
references: Genetics. 1995 Jun;140(2):527-35
references: 7498734
references: Genetics. 1974 May;77(1):95-104
references: 4858229
references: Nature. 2001 Sep 6;413(6851):70-4
references: 11544527
references: Matrix Biol. 2000 Jul;19(3):191-201
references: 10936444
references: Curr Opin Immunol. 2004 Feb;16(1):4-9
references: 14734103
references: Nature. 1999 Aug 26;400(6747):881-5
references: 10476968
references: J Biol Chem. 1998 Jan 2;273(1):600-5
references: 9417121
references: Cell. 1996 May 17;85(4):501-12
references: 8653786
references: J Cell Biol. 1984 Aug;99(2):615-27
references: 6746740
references: Neuron. 1992 Apr;8(4):677-89
references: 1314620
references: Cell. 1990 Nov 30;63(5):895-905
references: 2257628
references: Nature. 2004 Sep 30;431(7008):578-82
references: 15457263
references: J Physiol (Paris). 1990;84(1):78-81
references: 2193148
references: J Biol Chem. 1995 Feb 17;270(7):3392-9
references: 7852425
references: J Biol Chem. 2003 Aug 8;278(32):30106-14
references: 12773545
references: Mol Biol Cell. 1999 Oct;10(10):3205-21
references: 10512861
references: J Exp Biol. 1990 Oct;153:1-10
references: 2177765
references: J Biol Chem. 2001 Sep 28;276(39):36404-10
references: 11473126
references: Trends Cell Biol. 2006 Apr;16(4):198-205
references: 16515861
references: Nature. 2002 Jul 25;418(6896):417-22
references: 12140558
references: Nucleic Acids Res. 2003 Jul 1;31(13):3784-8
references: 12824418
references: Hum Mol Genet. 2003 Oct 15;12 Spec No 2:R259-64
references: 12925572
references: J Neurochem. 2002 Oct;83(2):271-84
references: 12423238
references: Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W332-5
references: 15215405
references: J Biol Chem. 1995 Feb 17;270(7):3378-84
references: 7531705
references: Bioinformatics. 2004 Feb 12;20(3):426-7
references: 14960472
references: Cell. 1996 May 17;85(4):525-35
references: 8653788
references: Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2227-31
references: 8460126
references: J Cell Biol. 2001 Mar 19;152(6):1219-32
references: 11257122
references: Science. 2000 Feb 11;287(5455):989-94
references: 10669422
references: Neuron. 1993 Sep;11(3):491-502
references: 8398142
references: Genetics. 1980 Aug;95(4):905-28
references: 7203008
references: J Cell Biol. 1986 Dec;103(6 Pt 1):2241-52
references: 3782297
references: Cell. 1996 May 17;85(4):513-23
references: 8653787
references: Cell. 1994 Jun 3;77(5):675-86
references: 8205617
references: Science. 2006 Jun 23;312(5781):1802-5
references: 16794080
references: Development. 2006 May;133(10):1911-21
references: 16611689
references: Cold Spring Harb Symp Quant Biol. 1990;55:407-18
references: 1966767
references: Neuron. 1999 May;23(1):33-44
references: 10402191
references: Cell. 1990 Sep 21;62(6):1041-52
references: 2401010
references: Nucleic Acids Res. 2006 Jan 1;34(Database issue):D257-60
references: 16381859
references: Neuron. 2002 Aug 1;35(3):489-505
references: 12165471
references: Nat Rev Mol Cell Biol. 2003 Apr;4(4):295-308
references: 12671652
references: Dev Biol. 2003 Apr 1;256(1):173-86
references: 12654300