PMID- 11071777
OWN - NLM
STAT- MEDLINE
DCOM- 20010104
LR  - 20071114
IS  - 0012-1606 (Print)
IS  - 0012-1606 (Linking)
VI  - 227
IP  - 2
DP  - 2000 Nov 15
TI  - Dystroglycan overexpression in vivo alters acetylcholine receptor aggregation at 
      the neuromuscular junction.
PG  - 595-605
AB  - Dystroglycan is a member of the transmembrane dystrophin glycoprotein complex in 
      muscle that binds to the synapse-organizing molecule agrin. Dystroglycan binding 
      and AChR aggregation are mediated by two separate domains of agrin. To test 
      whether dystroglycan plays a role in receptor aggregation at the neuromuscular 
      junction, we overexpressed it by injecting rabbit dystroglycan RNA into one- or 
      two-celled Xenopus embryos. We measured AChR aggregation in myotomes by labeling 
      them with rhodamine-alpha-bungarotoxin followed by confocal microscopy and image 
      analysis. Dystroglycan overexpression decreased AChR aggregation at the 
      neuromuscular junction. This result is consistent with dystroglycan competition 
      for agrin without signaling AChR aggregation. It also supports the hypothesis 
      that dystroglycan is not the myotube-associated specificity component, (MASC) a 
      putative coreceptor needed for agrin to activate muscle-specific kinase (MuSK) 
      and signal AChR aggregation. Dystroglycan was distributed along the surface of 
      muscle membranes, but was concentrated at the ends of myotomes, where AChRs 
      normally aggregate at synapses. Overexpressed dystroglycan altered AChR 
      aggregation in a rostral-caudal gradient, consistent with the sequential 
      development of neuromuscular synapses along the embryo. Increasing concentrations 
      of dystroglycan RNA did not further decrease AChR aggregation, but decreased 
      embryo survival. Development often stopped during gastrulation, suggesting an 
      essential, nonsynaptic role of dystroglycan during this early period of 
      development.
CI  - Copyright 2000 Academic Press.
FAU - Heathcote, R D
AU  - Heathcote RD
AD  - Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, 
      Wisconsin 53201, USA.
FAU - Ekman, J M
AU  - Ekman JM
FAU - Campbell, K P
AU  - Campbell KP
FAU - Godfrey, E W
AU  - Godfrey EW
LA  - eng
GR  - ES-04184/ES/NIEHS NIH HHS/United States
GR  - MH-57545/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Dev Biol
JT  - Developmental biology
JID - 0372762
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Luminescent Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Cholinergic)
RN  - 146888-27-9 (Dystroglycans)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Animals
MH  - Cytoskeletal Proteins/*genetics/*metabolism
MH  - Dystroglycans
MH  - Gene Expression
MH  - Gene Expression Regulation, Developmental
MH  - Green Fluorescent Proteins
MH  - Luminescent Proteins/genetics
MH  - Membrane Glycoproteins/*genetics/*metabolism
MH  - Microscopy, Confocal
MH  - Neuromuscular Junction/*embryology/*metabolism
MH  - *Receptor Aggregation
MH  - Receptors, Cholinergic/*metabolism
MH  - Synapses/metabolism
MH  - Xenopus laevis/embryology/genetics/metabolism
EDAT- 2000/11/10 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/11/10 11:00
PHST- 2000/11/10 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/11/10 11:00 [entrez]
AID - S0012-1606(00)99906-8 [pii]
AID - 10.1006/dbio.2000.9906 [doi]
PST - ppublish
SO  - Dev Biol. 2000 Nov 15;227(2):595-605. doi: 10.1006/dbio.2000.9906.