Mechanistic distinctions between agrin and laminin-1 induced aggregation of acetylcholine receptors.
BACKGROUND
One of the earliest steps in synaptogenesis at the neuromuscular junction is the aggregation of nicotinic acetylcholine receptors at the postsynaptic membrane. This study presents quantitative analyses of receptor and alpha-Dystroglycan aggregation in response to agrin and laminin-1, alone or in combination.


RESULTS
Both laminin and agrin increased overall expression of receptors on the plasma membrane. Following a 24 hour exposure, agrin increased the number of receptor aggregates but did not affect the number of alpha-Dystroglycan aggregates, while the reverse was true of laminin-1. Laminin also increased receptor concentration within aggregates, while agrin had no such effect. Finally, the spatial distribution of aggregates was indistinguishable from random in the case of laminin, while agrin induced aggregates were closer together than predicted by a random model.


CONCLUSIONS
Agrin and laminin-1 both increase acetylcholine receptor aggregate size after 24 hours, but several lines of evidence indicate that this is achieved via different mechanisms. Agrin and laminin had different effects on the number and density of receptor and alpha-Dystroglycan aggregates. Moreover the random distribution of laminin induced (as opposed to agrin induced) receptor aggregates suggests that the former may influence aggregate size by simple mass action effects due to increased receptor expression.
Lee
Lara K
LK
Békésy Laboratory of Neurobiology, University of Hawaii at Manoa, Honolulu, HI 96822, USA. laraklee@yahoo.com
Kunkel
Dennis D
DD
Stollberg
Jes
J
D018171:Agrin / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D049030:Dystroglycans; D007797:Laminin / Q000494:pharmacology*; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology; D011485:Protein Binding / Q000187:drug effects; D011940:Receptor Aggregation / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014982:Xenopus laevis
D018171:Agrin; D003598:Cytoskeletal Proteins; D007797:Laminin; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D011978:Receptors, Nicotinic; C121346:laminin 1; D049030:Dystroglycans