PMID- 16557298
OWN - NLM
STAT- MEDLINE
DCOM- 20060516
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 116
IP  - 4
DP  - 2006 Apr
TI  - Induction of myasthenia by immunization against muscle-specific kinase.
PG  - 1016-24
AB  - Muscle-specific kinase (MuSK) is critical for the synaptic clustering of 
      nicotinic acetylcholine receptors (AChRs) and plays multiple roles in the 
      organization and maintenance of neuromuscular junctions (NMJs). MuSK is activated 
      by agrin, which is released from motoneurons, and induces AChR clustering at the 
      postsynaptic membrane. Although autoantibodies against the ectodomain of MuSK 
      have been found in a proportion of patients with generalized myasthenia gravis 
      (MG), it is unclear whether MuSK autoantibodies are the causative agent of 
      generalized MG. In the present study, rabbits immunized with MuSK ectodomain 
      protein manifested MG-like muscle weakness with a reduction of AChR clustering at 
      the NMJs. The autoantibodies activated MuSK and blocked AChR clustering induced 
      by agrin or by mediators that do not activate MuSK. Thus MuSK autoantibodies 
      rigorously inhibit AChR clustering mediated by multiple pathways, an outcome that 
      broadens our general comprehension of the pathogenesis of MG.
FAU - Shigemoto, Kazuhiro
AU  - Shigemoto K
AD  - Department of Preventive Medicine, Ehime University School of Medicine, Ehime, 
      Japan. shigemot@m.ehime-u.ac.jp
FAU - Kubo, Sachiho
AU  - Kubo S
FAU - Maruyama, Naoki
AU  - Maruyama N
FAU - Hato, Naohito
AU  - Hato N
FAU - Yamada, Hiroyuki
AU  - Yamada H
FAU - Jie, Chen
AU  - Jie C
FAU - Kobayashi, Naoto
AU  - Kobayashi N
FAU - Mominoki, Katsumi
AU  - Mominoki K
FAU - Abe, Yasuhito
AU  - Abe Y
FAU - Ueda, Norifumi
AU  - Ueda N
FAU - Matsuda, Seiji
AU  - Matsuda S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060323
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Agrin)
RN  - 0 (Autoantibodies)
RN  - 0 (Receptors, Cholinergic)
RN  - 0 (Receptors, Nicotinic)
RN  - 0 (Recombinant Proteins)
RN  - EC 2.7.10.1 (MUSK protein, human)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 3.2.1.18 (Neuraminidase)
SB  - IM
MH  - Agrin/metabolism/pharmacology
MH  - Animals
MH  - Autoantibodies/*biosynthesis
MH  - Cells, Cultured
MH  - Enzyme Activation/immunology
MH  - Humans
MH  - Immunization
MH  - Mice
MH  - Models, Biological
MH  - Muscle Hypotonia/metabolism
MH  - Muscles/metabolism
MH  - Myasthenia Gravis/*etiology/immunology/metabolism
MH  - Neuraminidase/metabolism
MH  - Neuromuscular Junction/immunology
MH  - Protein Structure, Tertiary
MH  - Rabbits
MH  - Receptor Protein-Tyrosine Kinases/*immunology/metabolism
MH  - Receptors, Cholinergic/*immunology/metabolism
MH  - Receptors, Nicotinic/immunology/metabolism
MH  - Recombinant Proteins/genetics/metabolism
MH  - Signal Transduction
MH  - Species Specificity
PMC - PMC1409737
EDAT- 2006/03/25 09:00
MHDA- 2006/05/17 09:00
PMCR- 2006/04/03
CRDT- 2006/03/25 09:00
PHST- 2004/03/10 00:00 [received]
PHST- 2006/02/07 00:00 [accepted]
PHST- 2006/03/25 09:00 [pubmed]
PHST- 2006/05/17 09:00 [medline]
PHST- 2006/03/25 09:00 [entrez]
PHST- 2006/04/03 00:00 [pmc-release]
AID - 21545 [pii]
AID - 10.1172/JCI21545 [doi]
PST - ppublish
SO  - J Clin Invest. 2006 Apr;116(4):1016-24. doi: 10.1172/JCI21545. Epub 2006 Mar 23.