PMID- 18434415
OWN - NLM
STAT- MEDLINE
DCOM- 20080926
LR  - 20211020
IS  - 0950-1991 (Print)
IS  - 1477-9129 (Electronic)
IS  - 0950-1991 (Linking)
VI  - 135
IP  - 11
DP  - 2008 Jun
TI  - Essential roles of the acetylcholine receptor gamma-subunit in neuromuscular 
      synaptic patterning.
PG  - 1957-67
LID - 10.1242/dev.018119 [doi]
AB  - Formation of the vertebrate neuromuscular junction (NMJ) takes place in a 
      stereotypic pattern in which nerves terminate at select sarcolemmal sites often 
      localized to the central region of the muscle fibers. Several lines of evidence 
      indicate that the muscle fibers may initiate postsynaptic differentiation 
      independent of the ingrowing nerves. For example, nascent acetylcholine receptors 
      (AChRs) are pre-patterned at select regions of the muscle during the initial 
      stage of neuromuscular synaptogenesis. It is not clear how these pre-patterned 
      AChR clusters are assembled, and to what extent they contribute to pre- and 
      post-synaptic differentiation during development. Here, we show that genetic 
      deletion of the AChR gamma-subunit gene in mice leads to an absence of 
      pre-patterned AChR clusters during initial stages of neuromuscular 
      synaptogenesis. The absence of pre-patterned AChR clusters was associated with 
      excessive nerve branching, increased motoneuron survival, as well as aberrant 
      distribution of acetylcholinesterase (AChE) and rapsyn. However, clustering of 
      muscle specific kinase (MuSK) proceeded normally in the gamma-null muscles. AChR 
      clusters emerged at later stages owing to the expression of the AChR 
      epsilon-subunit, but these delayed AChR clusters were broadly distributed and 
      appeared at lower level compared with the wild-type muscles. Interestingly, 
      despite the abnormal pattern, synaptic vesicle proteins were progressively 
      accumulated at individual nerve terminals, and neuromuscular synapses were 
      ultimately established in gamma-null muscles. These results demonstrate that the 
      gamma-subunit is required for the formation of pre-patterned AChR clusters, which 
      in turn play an essential role in determining the subsequent pattern of 
      neuromuscular synaptogenesis.
FAU - Liu, Yun
AU  - Liu Y
AD  - Department of Neuroscience, UT Southwestern Medical Center, 5323 Harry Hines 
      Blvd, Dallas, TX 75235-9111, USA.
FAU - Padgett, Daniel
AU  - Padgett D
FAU - Takahashi, Masazumi
AU  - Takahashi M
FAU - Li, Hongqiao
AU  - Li H
FAU - Sayeed, Ayaz
AU  - Sayeed A
FAU - Teichert, Russell W
AU  - Teichert RW
FAU - Olivera, Baldomero M
AU  - Olivera BM
FAU - McArdle, Joseph J
AU  - McArdle JJ
FAU - Green, William N
AU  - Green WN
FAU - Lin, Weichun
AU  - Lin W
LA  - eng
GR  - R01 NS055028/NS/NINDS NIH HHS/United States
GR  - R01 NS055028-01A1/NS/NINDS NIH HHS/United States
GR  - NS055028/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080423
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (Muscle Proteins)
RN  - 0 (Receptors, Cholinergic)
RN  - 0 (peripheral membrane protein 43K)
RN  - EC 2.7.10.1 (MuSK protein, mouse)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 3.1.1.7 (Acetylcholinesterase)
SB  - IM
MH  - Acetylcholinesterase/metabolism
MH  - Animals
MH  - Cell Survival/genetics/physiology
MH  - Electrophysiology
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Motor Neurons/cytology/metabolism/physiology
MH  - Muscle Proteins/metabolism
MH  - Muscles/embryology/metabolism
MH  - Neuromuscular Junction/embryology/genetics/*metabolism
MH  - Organogenesis/genetics/*physiology
MH  - Receptor Protein-Tyrosine Kinases/metabolism
MH  - Receptors, Cholinergic/genetics/metabolism/*physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC2650015
MID - NIHMS93711
EDAT- 2008/04/25 09:00
MHDA- 2008/09/27 09:00
PMCR- 2009/03/03
CRDT- 2008/04/25 09:00
PHST- 2008/04/25 09:00 [pubmed]
PHST- 2008/09/27 09:00 [medline]
PHST- 2008/04/25 09:00 [entrez]
PHST- 2009/03/03 00:00 [pmc-release]
AID - dev.018119 [pii]
AID - 10.1242/dev.018119 [doi]
PST - ppublish
SO  - Development. 2008 Jun;135(11):1957-67. doi: 10.1242/dev.018119. Epub 2008 Apr 23.