MAP1B Light Chain Modulates Synaptic Transmission via AMPA Receptor Intracellular Trapping.
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2017
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Journal of Neuroscience
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Abstract
The regulated transport of AMPA-type glutamate receptors (AMPARs) to the synaptic membrane is a key mechanism to determine the
strength of excitatory synaptic transmission in the brain. In this work, we uncovered a new role for the microtubule-associated protein
MAP1B in modulating access of AMPARs to the postsynaptic membrane. Using mice and rats of either sex, we show that MAP1B light
chain (LC) accumulates in the somatodendritic compartment of hippocampal neurons, where it forms immobile complexes on microtubules
that limit vesicular transport. These complexes restrict AMPAR dendritic mobility, leading to the intracellular trapping of
receptors and impairing their access to the dendritic surface and spines. Accordingly, increasing MAP1B-LC expression depresses
AMPAR-mediated synaptic transmission. This effect is specific for the GluA2 subunit of the AMPAR and requires glutamate receptor
interacting protein 1 (GRIP1) interaction with MAP1B-LC. Therefore, MAP1B-LC represents an alternative link between GRIP1-AMPARs
and microtubules that does not result in productive transport, but rather limits AMPAR availability for synaptic insertion, with a direct
impact on synaptic transmission.
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Cytoskeleton, GluA1, GluA2, GRIP1, Hippocampus, Spine