PMID- 16675143
OWN - NLM
STAT- MEDLINE
DCOM- 20060928
LR  - 20191210
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 141
IP  - 1
DP  - 2006 Aug 11
TI  - The tetratricopeptide repeat domains of rapsyn bind directly to cytoplasmic 
      sequences of the muscle-specific kinase.
PG  - 87-100
AB  - Clustering of acetylcholine receptors at the developing vertebrate neuromuscular 
      junction is initiated by neural agrin, which stimulates the activity of the 
      muscle-specific kinase (MuSK). Acetylcholine receptor clustering is also 
      dependent on the postsynaptic scaffolding protein, rapsyn, which binds to 
      acetylcholine receptors. Here, we address the possibility that MuSK and rapsyn 
      bind directly to each other by coexpressing sequences of the cytoplasmic domain 
      of MuSK with rapsyn in COS-7 cells and assaying for codistribution and 
      biochemical interaction. Sequences constituting the bulk of the kinase domain can 
      interact with rapsyn. This interaction is mediated by the tetratricopeptide 
      repeat domains, but not the coiled coil or zinc finger domains, of rapsyn. This 
      interaction does not require tyrosine phosphorylation of the MuSK sequences. 
      Binding is direct, as indicated by blot overlay and surface plasmon resonance 
      experiments. The sequence of the cytoplasmic domain of MuSK that most effectively 
      codistributes with rapsyn confers the ability of an otherwise inactive receptor 
      tyrosine kinase, TrkA, to associate with rapsyn. Our results support a model in 
      which the tetratricopeptide repeat domains of rapsyn bind directly to the 
      cytoplasmic portion of MuSK, which could thereby serve as an initial scaffold for 
      the clustering of acetylcholine receptors.
FAU - Antolik, C
AU  - Antolik C
AD  - Department of Physiology, University of Maryland School of Medicine, 655 West 
      Baltimore Street, Baltimore, MD 21201, USA.
FAU - Catino, D H
AU  - Catino DH
FAU - Resneck, W G
AU  - Resneck WG
FAU - Bloch, R J
AU  - Bloch RJ
LA  - eng
GR  - R01 NS17282/NS/NINDS NIH HHS/United States
GR  - T32 AR007592/AR/NIAMS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20060503
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Muscle Proteins)
RN  - 0 (Peptides)
RN  - 0 (peripheral membrane protein 43K)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 2.7.10.1 (MuSK protein, mouse)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, trkC)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Binding Sites
MH  - Blotting, Western/methods
MH  - COS Cells
MH  - Chlorocebus aethiops
MH  - Cytoplasm/*metabolism
MH  - Fluorescent Antibody Technique/methods
MH  - Green Fluorescent Proteins/metabolism
MH  - Immunoprecipitation/methods
MH  - Microscopy, Confocal/methods
MH  - Muscle Proteins/*chemistry/*metabolism
MH  - Mutagenesis/physiology
MH  - Peptides/metabolism
MH  - Protein Binding/physiology
MH  - Protein Structure, Tertiary/physiology
MH  - Receptor Protein-Tyrosine Kinases/*chemistry/*metabolism
MH  - Receptor, trkC
MH  - Structure-Activity Relationship
MH  - Surface Plasmon Resonance/methods
MH  - Transfection/methods
EDAT- 2006/05/06 09:00
MHDA- 2006/09/29 09:00
CRDT- 2006/05/06 09:00
PHST- 2006/01/18 00:00 [received]
PHST- 2006/02/28 00:00 [revised]
PHST- 2006/03/16 00:00 [accepted]
PHST- 2006/05/06 09:00 [pubmed]
PHST- 2006/09/29 09:00 [medline]
PHST- 2006/05/06 09:00 [entrez]
AID - S0306-4522(06)00396-4 [pii]
AID - 10.1016/j.neuroscience.2006.03.035 [doi]
PST - ppublish
SO  - Neuroscience. 2006 Aug 11;141(1):87-100. doi: 10.1016/j.neuroscience.2006.03.035. 
      Epub 2006 May 3.