Deficient development and maintenance of postsynaptic specializations in mutant mice lacking an 'adult' acetylcholine receptor subunit.
At many synapses, 'fetal' neurotransmitter receptor subunits are replaced by 'adult' subunits as development proceeds. To assess the significance of such transitions, we deleted the gene encoding the adult acetylcholine receptor (AChR) epsilon subunit, which replaces its fetal counterpart, the gamma subunit, at the skeletal neuromuscular junction during early postnatal life. Several aspects of postnatal maturation, including synapse elimination, proceeded normally in the absence of the adult AChR, but structural development of the endplate was compromised. Later, inadequate compensation by the gamma subunit led to severely reduced AChR density in mutant endplates relative to controls. This decreased density led to a profound reorganization of AChR-associated components of the postsynaptic membrane and cytoskeleton. Together, these results suggest novel roles for AChRs in assembly of the postsynaptic apparatus.
Missias
A C
AC
Department of Molecular Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Mudd
J
J
Cunningham
J M
JM
Steinbach
J H
JH
Merlie
J P
JP
Sanes
J R
JR
D000818:Animals; D001665:Binding Sites; D002038:Bungarotoxins; D003598:Cytoskeletal Proteins / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D009045:Motor Endplate / Q000737:chemistry / Q000254:growth & development* / Q000502:physiology / Q000648:ultrastructure; D018908:Muscle Weakness / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D011950:Receptors, Cholinergic / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D013570:Synaptic Membranes / Q000737:chemistry / Q000502:physiology*
D002038:Bungarotoxins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D011950:Receptors, Cholinergic; D020794:Receptor Protein-Tyrosine Kinases