PMID- 19940021
OWN - NLM
STAT- MEDLINE
DCOM- 20100323
LR  - 20211020
IS  - 1939-4586 (Electronic)
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 21
IP  - 2
DP  - 2010 Jan 15
TI  - Caveolin-3 promotes nicotinic acetylcholine receptor clustering and regulates 
      neuromuscular junction activity.
PG  - 302-10
AB  - The molecular mechanisms that regulate the organization and activity of the 
      neuromuscular junction remain to be fully identified. Caveolae are invaginations 
      of the plasma membrane. Caveolin-3 is the structural protein component of 
      caveolae in muscle cells. We show that caveolin-3 is expressed at the 
      neuromuscular junction, that it associates with the nicotinic acetylcholine 
      receptor (nAChR), and that a lack of caveolin-3 inhibits clustering of the nAChR 
      in myotubes. At the molecular level, we demonstrate that caveolin-3 is a novel 
      muscle-specific kinase (MuSK) binding protein and that altered nAChR clustering 
      in caveolin-3-lacking myotubes results from inhibition of agrin-induced 
      phosphorylation/activation of MuSK and activation of Rac-1. Functional studies in 
      caveolin-3 null mice show abnormal neuromuscular junction activity that is 
      consistent with altered nAChR localization at the sarcolemma. Together, these 
      data identify caveolin-3 as a critical component of the signaling machinery that 
      drives nicotinic acetylcholine receptor clustering and controls neuromuscular 
      junction function.
FAU - Hezel, Michael
AU  - Hezel M
AD  - Department of Pharmacology and Chemical Biology, University of Pittsburgh School 
      of Medicine, Pittsburgh, PA 15261, USA.
FAU - de Groat, William C
AU  - de Groat WC
FAU - Galbiati, Ferruccio
AU  - Galbiati F
LA  - eng
GR  - T32-GM08424/GM/NIGMS NIH HHS/United States
GR  - R01 AG030636/AG/NIA NIH HHS/United States
GR  - R01-AG030636/AG/NIA NIH HHS/United States
GR  - R01 AG022548/AG/NIA NIH HHS/United States
GR  - T32 GM008424/GM/NIGMS NIH HHS/United States
GR  - R01-AG022548/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20091125
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (Agrin)
RN  - 0 (Caveolin 3)
RN  - 0 (Receptors, Nicotinic)
RN  - EC 2.7.10.1 (MuSK protein, mouse)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
SB  - IM
MH  - Agrin/pharmacology
MH  - Animals
MH  - Caveolin 3/deficiency/*metabolism
MH  - Cells, Cultured
MH  - Electromyography
MH  - Enzyme Activation/drug effects
MH  - Mice
MH  - Models, Biological
MH  - Muscle Contraction/drug effects
MH  - Muscle Fibers, Skeletal/cytology/drug effects/metabolism
MH  - Muscle, Skeletal/cytology/drug effects/metabolism
MH  - Neuromuscular Junction/drug effects/*metabolism
MH  - Protein Binding/drug effects
MH  - Receptor Protein-Tyrosine Kinases/metabolism
MH  - Receptors, Nicotinic/*metabolism
MH  - rac1 GTP-Binding Protein/metabolism
PMC - PMC2808226
EDAT- 2009/11/27 06:00
MHDA- 2010/03/24 06:00
PMCR- 2010/03/30
CRDT- 2009/11/27 06:00
PHST- 2009/11/27 06:00 [entrez]
PHST- 2009/11/27 06:00 [pubmed]
PHST- 2010/03/24 06:00 [medline]
PHST- 2010/03/30 00:00 [pmc-release]
AID - E09-05-0381 [pii]
AID - 3555555 [pii]
AID - 10.1091/mbc.e09-05-0381 [doi]
PST - ppublish
SO  - Mol Biol Cell. 2010 Jan 15;21(2):302-10. doi: 10.1091/mbc.e09-05-0381. Epub 2009 
      Nov 25.