Rapid recruitment of NMDA receptor transport packets to nascent synapses.
Although many of the molecules involved in synaptogenesis have been identified, the sequence and kinetics of synapse assembly in the central nervous system (CNS) remain largely unknown. We used simultaneous time-lapse imaging of fluorescent glutamate receptor subunits and presynaptic proteins in rat cortical neurons in vitro to determine the dynamics and time course of N-methyl-D-aspartate receptor (NMDAR) recruitment to nascent synapses. We found that both NMDA and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits are present in mobile transport packets in neurons before and during synaptogenesis. NMDAR transport packets are more mobile than AMPAR subunits, moving along microtubules at about 4 microm/min, and are recruited to sites of axodendritic contact within minutes. Whereas NMDAR recruitment to new synapses can be either concurrent with or independent of the protein PSD-95, AMPARs are recruited with a slower time course. Thus, glutamatergic synapses can form rapidly by the sequential delivery of modular transport packets containing glutamate receptors.
Washbourne
Philip
P
Center for Neuroscience, University of California Davis, 1544 Newton Ct., Davis, California 95616, USA.
Bennett
Jennie E
JE
McAllister
A Kimberley
AK
D000818:Animals; D002478:Cells, Cultured; D000076122:Disks Large Homolog 4 Protein; D005456:Fluorescent Dyes; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D008870:Microtubules / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D021122:Protein Subunits; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure
D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D005456:Fluorescent Dyes; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C033652:postsynaptic density proteins