16. November 2016

Joint research paper accepted for publication in Molecular Biology of the Cell

Ras and Rab interactor 1 controls neuronal plasticity by coordinating dendritic filopodial motility and AMPA receptor turnover

Ras and Rab interactor 1 controls neuronal plasticity by coordinating dendritic filopodial motility and AMPA receptor turnover

Zsófia Szíber 1, Hanna Liliom 1, Carlos O. Oueslati Morales 2, Attila Ignácz 1, Anikó Erika Rátkai 1, Kornelia Ellwanger 2, Gisela Link 2, Attila Szűcs 3, Angelika Hausser 2,4, Katalin Schlett 1,3

 

1Dept. Physiology and Neurobiology, Eötvös Loránd University, Budapest, Hungary

2Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany

3MTA-ELTE-NAP B - Neuronal Cell Biology Research Group, Budapest, Hungary

4Stuttgart Research Center Systems Biology, University of Stuttgart, Stuttgart, Germany

 

Abstract

Ras and Rab interactor 1 (RIN1) is predominantly expressed in the nervous system. RIN1 knockout animals have deficits in latent inhibition and fear extinction in the amygdala, suggesting a critical role for RIN1 in preventing the persistence of unpleasant memories. At the molecular level, RIN1 signals through Rab5 GTPases that control endocytosis of cell-surface receptors and Abl non-receptor tyrosine kinases that participate in actin cytoskeleton remodelling. Here, we report that RIN1 controls the plasticity of cultured mouse hippocampal neurons. Our results show that RIN1 affects the morphology of dendritic protrusions and accelerates dendritic filopodial motility through an Abl kinase dependent pathway. Lack of RIN1 results in enhanced mEPSC amplitudes indicating an increase in surface AMPA receptor levels compared to wild type neurons. We further provide evidence that the Rab5 GEF activity of RIN1 regulates surface GluA1 subunit endocytosis. Consequently, loss of RIN1 blocks surface AMPA receptor downregulation evoked by chemically induced long-term depression. Our findings indicate that RIN1 destabilizes synaptic connections and is a key player in postsynaptic AMPA receptor endocytosis, providing multiple ways of negatively regulating memory stabilisation during neuronal plasticity.

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