PMID- 22046365
OWN - NLM
STAT- MEDLINE
DCOM- 20120326
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 10
DP  - 2011
TI  - Mechanism of acetylcholine receptor cluster formation induced by DC electric 
      field.
PG  - e26805
LID - 10.1371/journal.pone.0026805 [doi]
LID - e26805
AB  - BACKGROUND: The formation of acetylcholine receptor (AChR) cluster is a key event 
      during the development of the neuromuscular junction. It is induced through the 
      activation of muscle-specific kinase (MuSK) by the heparan-sulfate proteoglycan 
      agrin released from the motor axon. On the other hand, DC electric field, a 
      non-neuronal stimulus, is also highly effective in causing AChRs to cluster along 
      the cathode-facing edge of muscle cells. METHODOLOGY/PRINCIPAL FINDINGS: To 
      understand its molecular mechanism, quantum dots (QDs) were used to follow the 
      movement of AChRs as they became clustered under the influence of electric field. 
      From analyses of trajectories of AChR movement in the membrane, it was concluded 
      that diffuse receptors underwent Brownian motion until they were immobilized at 
      sites of cluster formation. This supports the diffusion-mediated trapping model 
      in explaining AChR clustering under the influence of this stimulus. Disrupting 
      F-actin cytoskeleton assembly and interfering with rapsyn-AChR interaction 
      suppressed this phenomenon, suggesting that these are integral components of the 
      trapping mechanism induced by the electric field. Consistent with the idea that 
      signaling pathways are activated by this stimulus, the localization of 
      tyrosine-phosphorylated forms of AChR beta-subunit and Src was observed at cathodal 
      AChR clusters. Furthermore, disrupting MuSK activity through the expression of a 
      kinase-dead form of this enzyme abolished electric field-induced AChR clustering. 
      CONCLUSIONS: These results suggest that DC electric field as a physical stimulus 
      elicits molecular reactions in muscle cells in the form of cathodal MuSK 
      activation in a ligand-free manner to trigger a signaling pathway that leads to 
      cytoskeletal assembly and AChR clustering.
FAU - Zhang, Hailong Luke
AU  - Zhang HL
AD  - Division of Life Science and State Key Laboratory of Molecular Neuroscience, The 
      Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong 
      Kong.
FAU - Peng, H Benjamin
AU  - Peng HB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111025
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Agrin)
RN  - 0 (Receptors, Cholinergic)
RN  - 0 (Xenopus Proteins)
RN  - EC 2.7.10.1 (MuSK protein, Xenopus)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Agrin
MH  - Animals
MH  - Cells, Cultured
MH  - *Electric Stimulation
MH  - Muscle Cells/*chemistry/cytology
MH  - Neuromuscular Junction/*chemistry
MH  - Receptor Protein-Tyrosine Kinases/*metabolism
MH  - Receptors, Cholinergic/*metabolism
MH  - Signal Transduction
MH  - Static Electricity
MH  - Xenopus
MH  - Xenopus Proteins/*metabolism
PMC - PMC3201969
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2011/11/03 06:00
MHDA- 2012/03/27 06:00
PMCR- 2011/10/25
CRDT- 2011/11/03 06:00
PHST- 2011/08/01 00:00 [received]
PHST- 2011/10/04 00:00 [accepted]
PHST- 2011/11/03 06:00 [entrez]
PHST- 2011/11/03 06:00 [pubmed]
PHST- 2012/03/27 06:00 [medline]
PHST- 2011/10/25 00:00 [pmc-release]
AID - PONE-D-11-14863 [pii]
AID - 10.1371/journal.pone.0026805 [doi]
PST - ppublish
SO  - PLoS One. 2011;6(10):e26805. doi: 10.1371/journal.pone.0026805. Epub 2011 Oct 25.