Agrin acts via a MuSK receptor complex.
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.
Glass
David J
DJ
Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591, USA.
Bowen
David C
DC
Stitt
Trevor N
TN
Radziejewski
Czeslaw
C
Bruno
JoAnne
J
Ryan
Terence E
TE
Gies
David R
DR
Shah
Sonal
S
Mattsson
Karen
K
Burden
Steven J
SJ
DiStefano
Peter S
PS
Valenzuela
David M
DM
DeChiara
Thomas M
TM
Yancopoulos
G D
GD
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
D018171:Agrin; D011950:Receptors, Cholinergic; D014443:Tyrosine; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases