title: Agrin acts via a MuSK receptor complex.
abstract: Formation of th neuromuscular junction depends upon reciprocal inductive interactions between the developing nerve and muscle, resulting in the precise juxtaposition of a differentiated nerve terminal with a highly specialized patch on the muscle membrane, termed the motor endplate. Agrin is a nerve-derived factor that can induced molecular reorganizations at the motor endplate, but the mechanism of action of agrin remains poorly understood. MuSK is a receptor tyrosine kinase localized to the motor endplate, seemingly well positioned to receive a key nerve-derived signal. Mice lacking either agrin or MuSK have recently been generated and exhibit similarly profound defects in their neuromuscular junctions. Here we demonstrate that agrin acts via a receptor complex that includes MuSK as well as a myotube-specific accessory component.
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Glass
authors.forename: David C
authors.initials: DC
authors.lastname: Bowen
authors.forename: Trevor N
authors.initials: TN
authors.lastname: Stitt
authors.forename: Czeslaw
authors.initials: C
authors.lastname: Radziejewski
authors.forename: JoAnne
authors.initials: J
authors.lastname: Bruno
authors.forename: Terence E
authors.initials: TE
authors.lastname: Ryan
authors.forename: David R
authors.initials: DR
authors.lastname: Gies
authors.forename: Sonal
authors.initials: S
authors.lastname: Shah
authors.forename: Karen
authors.initials: K
authors.lastname: Mattsson
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Burden
authors.forename: Peter S
authors.initials: PS
authors.lastname: DiStefano
authors.forename: David M
authors.initials: DM
authors.lastname: Valenzuela
authors.forename: Thomas M
authors.initials: TM
authors.lastname: DeChiara
authors.forename: G D
authors.initials: GD
authors.lastname: Yancopoulos
mesh_terms: D018171:Agrin / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017353:Gene Deletion; D015870:Gene Expression / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000502:physiology / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology / Q000502:physiology; D009469:Neuromuscular Junction / Q000737:chemistry / Q000196:embryology / Q000502:physiology; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D018171:Agrin; D011950:Receptors, Cholinergic; D014443:Tyrosine; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases