PMID- 17565707
OWN - NLM
STAT- MEDLINE
DCOM- 20070906
LR  - 20131121
IS  - 1932-8451 (Print)
IS  - 1932-8451 (Linking)
VI  - 67
IP  - 8
DP  - 2007 Jul
TI  - L-type calcium channels mediate acetylcholine receptor aggregation on cultured 
      muscle.
PG  - 987-98
AB  - Agrin activation of muscle specific kinase (MuSK) initiates postsynaptic 
      development on skeletal muscle that includes the aggregation of acetylcholine 
      receptors (AChRs; Glass et al. [1996]: Cell 85: 513-523; Gautam et al. [1996]: 
      Cell 85: 525-535). Although the agrin/MuSK signaling pathway remains largely 
      unknown, changes in intracellular calcium levels are required for agrin-induced 
      AChR aggregation (Megeath and Fallon [1998]: J Neurosci 18: 672-678). Here, we 
      show that L-type calcium channels (L-CaChs) are required for full agrin-induced 
      aggregation of AChRs and sufficient to induce agrin-independent AChR aggregation. 
      Blockade of L-CaChs in muscle cultures inhibited agrin-induced AChR aggregation 
      but not tyrosine phosphorylation of MuSK or AChR beta subunits. Activation of 
      L-CaChs in the absence of agrin induced AChR aggregation but not tyrosine 
      phosphorylation of MuSK or AChR beta subunits. Agrin responsiveness was 
      significantly reduced in primary muscle cultures from the muscular dysgenesis 
      mouse, a natural mutant, which does not express the L-CaCh. Our results establish 
      a novel role for L-CaChs as important sources of the intracellular calcium 
      necessary for the aggregation of AChRs.
CI  - Copyright (c) 2007 Wiley Periodicals, Inc.
FAU - Milholland, Rebecca B R
AU  - Milholland RB
AD  - Department of Cell Biology and Anatomy, University of Arizona Health Sciences 
      Center, Tucson, Arizona 85724-5044, USA.
FAU - Dulla, Christopher
AU  - Dulla C
FAU - Gordon, Herman
AU  - Gordon H
LA  - eng
GR  - T35 HL07479/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Dev Neurobiol
JT  - Developmental neurobiology
JID - 101300215
RN  - 0 (Agrin)
RN  - 0 (Calcium Channels, L-Type)
RN  - 0 (Receptors, Cholinergic)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - EC 2.7.10.1 (MuSK protein, mouse)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - I9ZF7L6G2L (Nifedipine)
SB  - IM
MH  - Agrin/pharmacology
MH  - Animals
MH  - Calcium Channels, L-Type/drug effects/*physiology
MH  - Cells, Cultured
MH  - Genotype
MH  - Mice
MH  - Muscle, Skeletal/abnormalities/cytology/*physiology
MH  - Nifedipine/pharmacology
MH  - Phosphorylation
MH  - Phosphotyrosine/metabolism
MH  - Polymerase Chain Reaction
MH  - Rats
MH  - Receptor Protein-Tyrosine Kinases/metabolism
MH  - Receptors, Cholinergic/drug effects/*physiology
EDAT- 2007/06/15 09:00
MHDA- 2007/09/07 09:00
CRDT- 2007/06/15 09:00
PHST- 2007/06/15 09:00 [pubmed]
PHST- 2007/09/07 09:00 [medline]
PHST- 2007/06/15 09:00 [entrez]
AID - 10.1002/dneu.20397 [doi]
PST - ppublish
SO  - Dev Neurobiol. 2007 Jul;67(8):987-98. doi: 10.1002/dneu.20397.