The new Neuron has FIVE, count’em FIVE, articles on the protein, Arc. This protein gets made in all the right places and at all the right times to be important for synaptic plasticity and memory, but nobody knew what it did. Now we have clues that it might actually help pull AMPA-type glutamate receptors out of the membrane. One of the models presented suggests a role in setting the overall level of excitability allowed for a cell, so if some synapses are getting strengthed others have to take a hit. More later when I get a chance to really read. I recommend starting with the Tzingounis and Nicoll review.
Related; BDNF and Arc regulation: NMDARs vs AMPARs
Update: Upon finishing Chowdhury et al., I note that they found a ~2-fold increase in the amount of surface GluR1 (a subunit of the AMPA receptor) in neurons from the Arc knockout mouse, but in figure 4 of Plath et al. there is no change in basal synaptic transmission in these mouse. The only way I know to resolve this is for the surplus of AMPA receptors found by Chowdhury to be somewhere that they can’t affect transmission (i.e. not in the synapse).
Erratum: Rial Verde et al, citing the Chowdhury paper states that Arc interacts with the SH3 domain of endophilin. This is not the case. The experiment they performed on the basis of this statement is still okay because they are really just concerned with blocking the interaction between Arc and endophilin, but the domain of endophilin that Arc interacts with is a helix within the BAR domain which has a curved structure thought to normally interact with the curved lipid membrane of endocytic vesicles. (sorry for the jargon). Here’s some wikipedia for endocytosis. Check the clathrin-dependent kind, that’s how receptors are pulled out of the membrane. Pulling receptors out of the membrane would decrease the impact of neurotransmitter release, weakening the synapse.
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