Subsynaptic positioning of AMPARs by LRRTM2 controls synaptic strength
AdvisorBlanpied, Thomas A.
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AbstractRecent evidence suggests that the nanoscale organization of proteins within synapses may control the strength of communication between neurons in the brain. The unique subsynaptic distribution of glutamate receptors, which cluster in nano-alignment with presynaptic sites of glutamate release, supports this idea. However, testing it has been difficult because mechanisms controlling this subsynaptic organization remain unknown. Reasoning that transcellular interactions could influence AMPAR positioning, we targeted a key transsynaptic adhesion molecule implicated in controlling AMPAR number at synapses, LRRTM2, using engineered, rapid proteolysis. Severing the LRRTM2 extracellular domain led quickly to nanoscale de-clustering of AMPARs away from release sites, not prompting their escape from synapses until much later. This rapid remodeling of AMPAR position produced significant deficits in evoked, but not spontaneous, postsynaptic receptor activation. These results dissociate receptor number within synapses from their nano-positioning in determination of synaptic function and support the novel concept that adhesion molecules acutely position AMPA receptors to dynamically control synaptic strength.
DescriptionUniversity of Maryland, Baltimore. Physiology, Ph.D. 2021
Cell Adhesion Molecules