PMID- 16219760
OWN - NLM
STAT- MEDLINE
DCOM- 20060207
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 280
IP  - 50
DP  - 2005 Dec 16
TI  - Conjugation of LG domains of agrins and perlecan to polymerizing laminin-2 
      promotes acetylcholine receptor clustering.
PG  - 41449-57
AB  - Neuromuscular junction (NMJ) assembly is characterized by the clustering and 
      neuronal alignment of acetylcholine receptors (AChRs). In this study we have 
      addressed post-synaptic contributions to assembly that may arise from the NMJ 
      basement membrane with cultured myotubes. We show that the cell surface-binding 
      LG domains of non-neural (muscle) agrin and perlecan promote AChR clustering in 
      the presence of laminin-2. This type of AChR clustering occurs with a several 
      hour lag, requires muscle-specific kinase (MuSK), and is accompanied by tyrosine 
      phosphorylation of MuSK and betaAChR. It also requires conjugation of the agrin 
      or perlecan to laminin together with laminin polymerization. Furthermore, AChR 
      clustering can be mimicked with antibody binding to non-neural agrin, supporting 
      a mechanism of ligand aggregation. Neural agrin, in addition to its unique 
      ability to cluster AChRs through its B/z sequence insert, also exhibits 
      laminin-dependent AChR clustering, the latter enhancing and stabilizing its 
      activity. Finally, we show that type IV collagen, which lacks clustering activity 
      on its own, stabilizes laminin-dependent AChR clusters. These findings provide 
      evidence for cooperative and partially redundant MuSK-dependent functions of 
      basement membrane in AChR assembly that can enhance neural agrin activity yet 
      operate in its absence. Such interactions may contribute to the assembly of 
      aneural AChR clusters that precede neural agrin release as well as affect later 
      NMJ development.
FAU - Smirnov, Sergei P
AU  - Smirnov SP
AD  - Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical 
      School, Piscataway, New Jersey 08854, USA.
FAU - Barzaghi, Patrizia
AU  - Barzaghi P
FAU - McKee, Karen K
AU  - McKee KK
FAU - Ruegg, Markus A
AU  - Ruegg MA
FAU - Yurchenco, Peter D
AU  - Yurchenco PD
LA  - eng
GR  - R01 NS038469/NS/NINDS NIH HHS/United States
GR  - R01-NS38469/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20051011
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Agrin)
RN  - 0 (DNA, Complementary)
RN  - 0 (Heparan Sulfate Proteoglycans)
RN  - 0 (Laminin)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Polymers)
RN  - 0 (Receptors, Cholinergic)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (nidogen)
RN  - 143972-95-6 (perlecan)
RN  - 42HK56048U (Tyrosine)
SB  - IM
MH  - Agrin/*chemistry
MH  - Animals
MH  - Basement Membrane/metabolism
MH  - Cell Membrane/metabolism
MH  - Chickens
MH  - Cluster Analysis
MH  - DNA, Complementary/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Genetic Techniques
MH  - Heparan Sulfate Proteoglycans/*chemistry
MH  - Laminin/chemistry/metabolism
MH  - Membrane Glycoproteins/chemistry
MH  - Mice
MH  - Models, Biological
MH  - Muscle Cells/metabolism
MH  - Muscle Fibers, Skeletal/metabolism
MH  - Neuromuscular Junction/metabolism
MH  - Neurons/metabolism
MH  - Phosphorylation
MH  - Polymers/*chemistry
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - Receptors, Cholinergic/*chemistry
MH  - Recombinant Fusion Proteins/chemistry
MH  - Synapses/metabolism
MH  - Time Factors
MH  - Tyrosine/chemistry
EDAT- 2005/10/13 09:00
MHDA- 2006/02/08 09:00
CRDT- 2005/10/13 09:00
PHST- 2005/10/13 09:00 [pubmed]
PHST- 2006/02/08 09:00 [medline]
PHST- 2005/10/13 09:00 [entrez]
AID - S0021-9258(20)58954-0 [pii]
AID - 10.1074/jbc.M508939200 [doi]
PST - ppublish
SO  - J Biol Chem. 2005 Dec 16;280(50):41449-57. doi: 10.1074/jbc.M508939200. Epub 2005 
      Oct 11.