Agrin controls synaptic differentiation in hippocampal neurons.
Agrin controls the formation of the neuromuscular junction. Whether it regulates the differentiation of other types of synapses remains unclear. Therefore, we have studied the role of agrin in cultured hippocampal neurons. Synaptogenesis was severely compromised when agrin expression or function was suppressed by antisense oligonucleotides and specific antibodies. The effects of antisense oligonucleotides were found to be highly specific because they were reversed by adding recombinant agrin and could not be detected in cultures from agrin-deficient animals. Interestingly, the few synapses formed in reduced agrin conditions displayed diminished vesicular turnover, despite a normal appearance at the EM level. Thus, our results demonstrate the necessity of agrin for synaptogenesis in hippocampal neurons.
Bose
C M
CM
Department of Neuroscience, The Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA.
Qiu
D
D
Bergamaschi
A
A
Gravante
B
B
Bossi
M
M
Villa
A
A
Rupp
F
F
Malgaroli
A
A
D018171:Agrin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004558:Electric Stimulation; D004705:Endocytosis / Q000187:drug effects; D005071:Evoked Potentials / Q000187:drug effects; D005089:Exocytosis / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013572:Synaptic Vesicles / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
D018171:Agrin; D000906:Antibodies; C409466:NR1 NMDA receptor; D016376:Oligonucleotides, Antisense; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D013779:Tetrodotoxin