The role of an agrin-growth factor interaction in ACh receptor clustering.
The clustering of acetylcholine receptors (AChRs) at the neuromuscular junction is mediated in part by the heparan-sulfate proteoglycan agrin. However, our previous studies have also suggested the role of heparin-binding growth-associated molecular (HB-GAM) in AChR clustering. Here the role of an agrin-HB-GAM interaction in this process was examined using cultured Xenopus muscle cells. Agrin-coated beads further treated with HB-GAM were highly effective in AChR cluster induction. Protein overlay assays showed specific binding of HB-GAM to agrin. In addition, agrin-enriched neuritic tracks bound HB-GAM in a manner that showed a high degree of colocalization between the neural agrin and the applied factor. Finally, the introduction of exogenous HB-GAM together with soluble agrin resulted in the appearance of AChR clusters on the dorsal surface of cells in an agrin isoform-dependent manner; a dramatic change from the characteristic ventral AChR clustering seen in response to agrin alone. These results suggest that agrin may mediate AChR clustering by interacting with muscle-bound heparin-binding growth factors such as HB-GAM.
Daggett
D F
DF
Neurobiology Curriculum and Department of Cell Biology and Anatomy, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Cohen
M W
MW
Stone
D
D
Nikolics
K
K
Rauvala
H
H
Peng
H B
HB
D018171:Agrin / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D004357:Drug Synergism; D006133:Growth Substances / Q000502:physiology*; D015151:Immunoblotting; D008863:Microspheres; D009434:Neural Pathways / Q000378:metabolism; D016501:Neurites / Q000502:physiology; D011940:Receptor Aggregation; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000502:physiology*; D013499:Surface Properties; D014981:Xenopus / Q000196:embryology
D018171:Agrin; D002352:Carrier Proteins; D016207:Cytokines; D006133:Growth Substances; D011950:Receptors, Cholinergic; C066845:pleiotrophin