Loss of hnRNP K impairs synaptic plasticity in hippocampal neurons

Alessandra Folci; Lisa Mapelli; Jenny Sassone; Francesca Prestori; Egidio D'Angelo; Silvia Bassani; Maria Passafaro

doi:10.1523/JNEUROSCI.0303-14.2014

Loss of hnRNP K impairs synaptic plasticity in hippocampal neurons

J Neurosci. 2014 Jul 2;34(27):9088-95. doi: 10.1523/JNEUROSCI.0303-14.2014.

Authors

Alessandra Folci¹, Lisa Mapelli², Jenny Sassone³, Francesca Prestori⁴, Egidio D'Angelo⁵, Silvia Bassani⁶, Maria Passafaro⁶

Affiliations

¹ CNR Institute of Neuroscience, Department of Medical Biotechnology and Translational Medicine (BIOMETRA), University of Milan, Milan 20129, Italy.
² CNR Institute of Neuroscience, Department of Medical Biotechnology and Translational Medicine (BIOMETRA), University of Milan, Milan 20129, Italy, Department of Brain and Behavioral Sciences, Neurophysiology Unit, University of Pavia, Pavia 27100, Italy, Brain Connectivity Center, C. Mondino National Neurological Institute, Pavia 27100, Italy, and.
³ IRCCS Istituto Auxologico Italiano, Department of Neurology and Laboratory of Neuroscience, Milan 20095, Italy.
⁴ Department of Brain and Behavioral Sciences, Neurophysiology Unit, University of Pavia, Pavia 27100, Italy.
⁵ Department of Brain and Behavioral Sciences, Neurophysiology Unit, University of Pavia, Pavia 27100, Italy, Brain Connectivity Center, C. Mondino National Neurological Institute, Pavia 27100, Italy, and.
⁶ CNR Institute of Neuroscience, Department of Medical Biotechnology and Translational Medicine (BIOMETRA), University of Milan, Milan 20129, Italy, [email protected] [email protected].

Abstract

Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is an RNA-binding protein implicated in RNA metabolism. Here, we investigated the role of hnRNP K in synapse function. We demonstrated that hnRNP K regulates dendritic spine density and long-term potentiation (LTP) in cultured hippocampal neurons from embryonic rats. LTP requires the extracellular signal-regulated kinase (ERK)1/2-mediated phosphorylation and cytoplasmic accumulation of hnRNP K. Moreover, hnRNP K knockdown prevents ERK cascade activation and GluA1-S845 phosphorylation and surface delivery, which are essential steps for LTP. These findings establish hnRNP K as a new critical regulator of synaptic transmission and plasticity in hippocampal neurons.

Keywords: LTP; dendritic spines; hnRNP K; neurons; synapse.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Calcium Signaling
Cells, Cultured
Dendrites / ultrastructure
Female
Gene Expression Regulation / drug effects
Gene Expression Regulation / physiology
Hippocampus / cytology
Long-Term Potentiation / physiology*
MAP Kinase Signaling System
Male
Nerve Tissue Proteins / antagonists & inhibitors
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / physiology*
Neurons / physiology
Neurons / ultrastructure
Phosphorylation
Protein Processing, Post-Translational
Protein Transport
RNA Interference
RNA, Small Interfering / pharmacology
Rats
Receptors, AMPA / metabolism
Ribonucleoproteins / antagonists & inhibitors
Ribonucleoproteins / genetics
Ribonucleoproteins / physiology*
Synaptic Transmission / physiology*
Transfection

Substances

Hnrnpk protein, rat
Nerve Tissue Proteins
RNA, Small Interfering
Receptors, AMPA
Ribonucleoproteins
glutamate receptor ionotropic, AMPA 1

Grants and funding

TCP01014/TI_/Telethon/Italy