Rapid Activity-Driven SNARE-Dependent Trafficking of Nicotinic Receptors on Somatic Spines

Abstract

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 ␣7 subunits are widely expressed in the nervous system and allow calcium influx. Because of this, ␣7-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. SNAREdependent 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 ␣7-receptor responses and downstream signaling.

An Acute Effect of Neuregulin 1β to Suppress α7-Containing Nicotinic Acetylcholine Receptors in Hippocampal Interneurons

“…A more likely explanation involves a change in the balance of receptor endocytosis and exocytosis. nAChRs undergo rapid trafficking between the surface membrane and intracellular pools (Liu et al, 2005). Trafficking is supported by our results after treatment with phalloidin and cyt D. It is also supported by the rapid decrease in the surface Alexa488-␣Bgt binding sites detected by confocal microscopy.…”

“…The actin cytoskeleton and spine integrity as well as SNARE are required for nAChRs trafficking in the chick neurons ( Shoop et al, 2000;Liu et al, 2005). The specificity for ␣7 subunits observed in our studies of NRG ␤1 was evident in untreated chick neurons (Liu et al, 2005) and in oocytes expressing nicotinic receptor subunits (Cho et al, 2005).…”

“…Rapid trafficking of ␣7 nAChRs also occurs in spines that extend from chick ciliary ganglion neuron somata (Liu et al, 2005). The actin cytoskeleton and spine integrity as well as SNARE are required for nAChRs trafficking in the chick neurons ( Shoop et al, 2000;Liu et al, 2005).…”

Apoptotic surface delivery of K+ channels

“…Scale bars: 5 nA, 25 ms. (b) Percent of new Kv2.1(I379C) channels present in CON and AP neurons, calculated from the ratio of current density before and after the second MTSET exposure (n ¼ 8; *Po0.05) albeit all of them being ligand-gated ion channels. [20][21][22][23] Our results indicate that the same t-SNARE proteins that mediate neurotransmission at nerve terminals support exocytotic delivery of somatodendritic K þ channels during neuronal apoptosis.…”

Olfactory habituation: Fresh insights from flies

“…Recent work has implicated down-regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors at excitatory synapses in LTH in Caenorhabditis elegans and Aplysia (3, 8). ACh, not glutamate, is the major excitatory transmitter in the insect brain; however, rapid trafficking of nicotinic ACh receptors in the nervous system has been reported (15), and possibly downregulation of ACh receptors at excitatory synapses in the fly's olfactory system contributes to olfactory habituation. The existence of multiple mechanisms of habituation would be consistent with emerging evidence from studies of habituation in other systems (3,8,16,17).…”