A retention-release mechanism based on RAB11FIP2 for AMPA receptor synaptic delivery during long-term potentiation
| Autor: | Silvia Gutiérrez-Eisman, María Royo, Sandra Jurado, José A. Esteban, Raquel Jiménez, Mónica Fernández-Monreal, Yolanda Gutiérrez |
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| Přispěvatelé: | Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Instituto de Salud Carlos III, Ministerio de Educación, Cultura y Deporte (España), Agencia Estatal de Investigación (España) |
| Rok vydání: | 2019 |
| Předmět: |
Male
Dendritic spine Endosome Recycling endosomes Dendritic Spines Long-Term Potentiation Endosomes AMPA receptor Membrane trafficking Hippocampal formation Biology Hippocampus Synaptic plasticity Dephosphorylation 03 medical and health sciences 0302 clinical medicine LTP induction Animals Receptors AMPA Rats Wistar 030304 developmental biology 0303 health sciences musculoskeletal neural and ocular physiology Membrane Proteins Long-term potentiation Cell Biology Rats Cell biology nervous system Synapses Female LTP Carrier Proteins 030217 neurology & neurosurgery |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | It is well-established that Rab11-dependent recycling endosomes drive the activity-dependent delivery of AMPA receptors (AMPARs) into synapses during long-term potentiation (LTP). Nevertheless, the molecular basis for this specialized function of recycling endosomes is still unknown. Here, we have investigated RAB11FIP2 (FIP2 hereafter) as a potential effector of Rab11-dependent trafficking during LTP in rat hippocampal slices. Surprisingly, we found that FIP2 operates independently from Rab11 proteins, and acts as a negative regulator of AMPAR synaptic trafficking. Under basal conditions, FIP2 associates with AMPARs at immobile compartments, separately from recycling endosomes. Using shRNA-mediated knockdown, we found that FIP2 prevents GluA1 (encoded by the Gria1 gene) AMPARs from reaching the surface of dendritic spines in the absence of neuronal stimulation. Upon induction of LTP, FIP2 is rapidly mobilized, dissociates from AMPARs and undergoes dephosphorylation. Interestingly, this dissociation of the FIP2¿AMPAR complex, together with FIP2 dephosphorylation, is required for LTP, but the interaction between FIP2 and Rab11 proteins is not. Based on these results, we propose a retention¿release mechanism, where FIP2 acts as a gate that restricts the trafficking of AMPARs, until LTP induction triggers their release and allows synaptic delivery. Ministerio de Ciencia, Innovación y Universidades (Spanish Ministry of Science, Innovation and Universities) (SAF2015-72988-EXP, SAF2017-86983-R) and the European Union Joint Programming Initiative A healthy diet for a healthy life (PCIN-2016-095). M.R. and Y.G. were recipients of pre-doctoral contracts from the Instituto de Salud Carlos III and from the Ministerio de Educación, Cultura y Deporte (Spanish Ministry of Education, Culture and Sport) |
| Databáze: | OpenAIRE |
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