Publication Date:
1997-04-25
Description:
ARIA (for acetylcholine receptor-inducing activity), a protein purified on the basis of its ability to stimulate acetylcholine receptor (AChR) synthesis in cultured myotubes, is a member of the neuregulin family and is present at motor endplates. This suggests an important role for neuregulins in mediating the nerve-dependent accumulation of AChRs in the postsynaptic membrane. Nerve-muscle synapses have now been analyzed in neuregulin-deficient animals. Mice that are heterozygous for the deletion of neuregulin isoforms containing an immunoglobulin-like domain are myasthenic. Postsynaptic AChR density is significantly reduced, as judged by the decrease in the mean amplitude of spontaneous miniature endplate potentials and bungarotoxin binding. On the other hand, the mean amplitude of evoked endplate potentials was not decreased, due to an increase in the number of quanta released per impulse, a compensation that has been observed in other myasthenic states. Thus, the density of AChRs in the postsynaptic membrane depends on immunoglobulin-containing neuregulin isoforms throughout the life of the animal.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sandrock, A W Jr -- Dryer, S E -- Rosen, K M -- Gozani, S N -- Kramer, R -- Theill, L E -- Fischbach, G D -- K08-NS01580/NS/NINDS NIH HHS/ -- R01-NS18458/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1997 Apr 25;276(5312):599-603.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9110980" target="_blank"〉PubMed〈/a〉
Keywords:
Acetylcholine/metabolism
;
Animals
;
Bungarotoxins/metabolism
;
Glycoproteins/genetics/*physiology
;
Heterozygote
;
Immunoglobulins/analysis
;
In Vitro Techniques
;
Membrane Potentials
;
Mice
;
Motor Endplate/metabolism/physiology
;
Muscle Weakness/etiology
;
Nerve Tissue Proteins/genetics/*physiology
;
Neuregulin-1
;
Neuregulins
;
Neuromuscular Junction/*metabolism
;
Receptors, Cholinergic/genetics/*metabolism
;
Synaptic Transmission
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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