Rapid activity-driven SNARE-dependent trafficking of nicotinic receptors on somatic spines.
Rapid trafficking of glutamate receptors contributes importantly to synaptic plasticity, but whether similar trafficking extends to other ionotropic receptors is unknown. Nicotinic acetylcholine receptors containing alpha7 subunits are widely expressed in the nervous system and allow calcium influx. Because of this, alpha7-containing receptors regulate diverse events, depending on the signaling pathways available. We find that the receptors codistribute with target soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) postsynaptically and that nicotinic stimulation rapidly induces SNARE-dependent vesicular endocytosis accompanied by receptor internalization. At the same time, a SNARE-dependent process recruits receptors to the cell surface from internal pools. Overall, the trafficking does not markedly change the number of surface receptors or their combined whole-cell response to nicotine. SNARE-dependent trafficking is needed, however, for the receptors to remain capable of activating the transcription factor cAMP response element-binding protein and attendant gene expression when repeatedly challenged. Thus, trafficking appears to be essential for maintaining functional coupling between alpha7-receptor responses and downstream signaling.
Liu
Zhaoping
Z
Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093-0357, USA.
Tearle
Adam W
AW
Nai
Qiang
Q
Berg
Darwin K
DK
D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured / Q000378:metabolism; D002642:Chick Embryo; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D005726:Ganglia, Parasympathetic / Q000166:cytology / Q000196:embryology; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D021381:Protein Transport; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D050600:SNARE Proteins; D015398:Signal Transduction / Q000502:physiology; D033921:Vesicular Transport Proteins / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; D011993:Recombinant Fusion Proteins; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; D064569:alpha7 Nicotinic Acetylcholine Receptor; C096325:botulinum toxin type D; D009538:Nicotine; D001905:Botulinum Toxins; C096324:botulinum toxin type C; D002118:Calcium