Functions of agrin and agrin-related proteins.
Agrin, a molecule produced by motoneurons that induces the aggregation of nicotinic acetylcholine receptors (nAChRs), has recently been structurally characterized. Agrin-related proteins (ARPs) that arise from differential splicing are synthesized by neurons and muscle. The C-terminal region of agrin that instructs muscle to aggregate nAChRs contains three laminin A modules separated by epidermal growth factor-like modules. Alternative splicing in the laminin A modules leads to the formation of at least three ARPs that are devoid of nAChR-aggregating activity. In their N-terminal regions, both agrin and ARPs contain nine follistatin-related modules that, like those in follistatin and in another related protein, osteonectin, may have the capability to bind members of the transforming growth factor beta (TGF-beta) or platelet-derived growth factor (PDGF) families. This review proposes that these follistatin-like regions of agrin and ARPs might bind and localize growth factors, and thus provide a matrix-bound concentration of them. Beyond agrin's role in inducing AChR aggregation, the function of agrin and ARPs to provide a localized reservoir of growth factors could contribute to the formation and maintenance of the long-lasting synaptic architecture by specifying and limiting the area of influence of these molecules.
Patthy
L
L
Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest.
Nikolics
K
K
D018171:Agrin; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002645:Chickens / Q000235:genetics; D016384:Consensus Sequence; D003545:Cysteine; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000502:physiology*; D006133:Growth Substances / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009469:Neuromuscular Junction / Q000378:metabolism; D011487:Protein Conformation; D051381:Rats / Q000235:genetics; D011940:Receptor Aggregation; D017978:Receptors, Growth Factor; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D012091:Repetitive Sequences, Nucleic Acid; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014101:Torpedo / Q000235:genetics
D018171:Agrin; D016326:Extracellular Matrix Proteins; D006133:Growth Substances; D009419:Nerve Tissue Proteins; D017978:Receptors, Growth Factor; D017981:Receptors, Neurotransmitter; C080030:agrin receptor; D003545:Cysteine