Laminin-induced acetylcholine receptor clustering: an alternative pathway.
The induction of acetylcholine receptor (AChR) clustering by neurally released agrin is a critical, early step in the formation of the neuromuscular junction. Laminin, a component of the muscle fiber basal lamina, also induces AChR clustering. We find that induction of AChR clustering in C2 myotubes is specific for laminin-1; neither laminin-2 (merosin) nor laminin-11 (a synapse-specific isoform) are active. Moreover, laminin-1 induces AChR clustering by a pathway that is independent of that used by neural agrin. The effects of laminin-1 and agrin are strictly additive and occur with different time courses. Most importantly, laminin- 1-induced clustering does not require MuSK, a receptor tyrosine kinase that is part of the receptor complex for agrin. Laminin-1 does not cause tyrosine phosphorylation of MuSK in C2 myotubes and induces AChR clustering in myotubes from MuSK-/- mice that do not respond to agrin. In contrast to agrin, laminin-1 also does not induce tyrosine phosphorylation of the AChR, demonstrating that AChR tyrosine phosphorylation is not required for clustering in myotubes. Laminin-1 thus acts by a mechanism that is independent of that used by agrin and may provide a supplemental pathway for AChR clustering during synaptogenesis.
Sugiyama
J E
JE
National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
Glass
D J
DJ
Yancopoulos
G D
GD
Hall
Z W
ZW
D018171:Agrin / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D007797:Laminin / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009132:Muscles / Q000166:cytology; D010766:Phosphorylation; D051381:Rats; D011940:Receptor Aggregation / Q000187:drug effects; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D018171:Agrin; D007797:Laminin; D011950:Receptors, Cholinergic; D014443:Tyrosine; D020794:Receptor Protein-Tyrosine Kinases