Differing mechanisms for glutamate receptor aggregation on dendritic spines and shafts in cultured hippocampal neurons.
We have explored the ability of axons from spinal and hippocampal neurons to aggregate NMDA- and AMPA-type glutamate receptors on each other as a way of exploring the molecular differences between their presynaptic elements. Spinal axons, which normally cluster only AMPA-type glutamate receptors on other spinal neurons, cluster both AMPA- and NMDA-type glutamate receptors on the dendritic shafts of hippocampal interneurons but are ineffective at clustering either subtype of glutamate receptor on the dendritic spines of hippocampal pyramidal neurons. Conversely, hippocampal axons appear to be multipotent, capable of clustering both AMPA- and NMDA-type glutamate receptors on hippocampal interneurons and pyramidal cells. The secretion of the neuronal activity-regulated pentraxin (Narp) by hippocampal axons is restricted to contacts with interneurons. Exogenous application of Narp to cultured hippocampal neurons results in clusters of both NMDA- and AMPA-type glutamate receptors on hippocampal interneurons but not hippocampal pyramidal neurons. Because Narp displays no ability to directly aggregate NMDA receptors, we propose that Narp aggregates NMDA receptors in hippocampal interneurons indirectly through cytoplasmic coupling to synaptic AMPA receptors. Furthermore, our data suggest the existence of a novel molecule(s), capable of forming excitatory synapses on dendritic spines.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Ruifa
R
Mi
Xiaopei
X
Tang
Ralph
R
Sutter
Desheng
D
Xu
Paul
P
Worley
Richard J
RJ
O'Brien
D000818:Animals; D001369:Axons / Q000378:metabolism; D002097:C-Reactive Protein / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D005799:Genes, Dominant; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007395:Interneurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011940:Receptor Aggregation / Q000502:physiology*; D018091:Receptors, AMPA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D014162:Transfection; D000099153:Pentraxins
D002097:C-Reactive Protein; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D000099153:Pentraxins