TY - JOUR T1 - MAP1B light chain modulates synaptic transmission via AMPA receptor intracellular trapping JF - The Journal of Neuroscience JO - J. Neurosci. DO - 10.1523/JNEUROSCI.0505-17.2017 SP - 0505-17 AU - Rocío Palenzuela AU - Yolanda Gutiérrez AU - Jonathan E. Draffin AU - Argentina Lario AU - Marion Benoist AU - José A. Esteban Y1 - 2017/09/13 UR - http://www.jneurosci.org/content/early/2017/09/13/JNEUROSCI.0505-17.2017.abstract N2 - 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 the 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 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.SIGNIFICANCE STATEMENTThe ability of neurons to modify their synaptic connections, known as synaptic plasticity, is accepted as the cellular basis for learning and memory. One mechanism for synaptic plasticity is the regulated addition and removal of AMPA-type glutamate receptors at excitatory synapses. In this study we describe that a microtubule-associated protein, MAP1B light chain (MAP1B-LC) participates in this process. MAP1B-LC forms immobile complexes along dendrites. These complexes limit intracellular vesicular trafficking and trap AMPA receptors inside the dendritic shaft. In this manner, MAP1B restricts the access of AMPA receptors to dendritic spines and the postsynaptic membrane, contributing to down-regulate synaptic transmission. ER -