BDNF-induced local translation of GluA1 is regulated by HNRNP A2/B1

Science Advances
Youngseob JungKyong-Tai Kim

Abstract

The AMPA receptor subunit GluA1 is essential for induction of synaptic plasticity. While various regulatory mechanisms of AMPA receptor expression have been identified, the underlying mechanisms of GluA1 protein synthesis are not fully understood. In neurons, axonal and dendritic mRNAs have been reported to be translated in a cap-independent manner. However, molecular mechanisms of cap-independent translation of synaptic mRNAs remain largely unknown. Here, we show that GluA1 mRNA contains an internal ribosome entry site (IRES) in the 5'UTR. We also demonstrate that heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 interacts with GluA1 mRNA and mediates internal initiation of GluA1 Brain-derived neurotrophic factor (BDNF) stimulation increases IRES-mediated GluA1 translation via up-regulation of HNRNP A2/B1. Moreover, BDNF-induced GluA1 expression and dendritic spine density were significantly decreased in neurons lacking hnRNP A2/B1. Together, our data demonstrate that IRES-mediated translation of GluA1 mRNA is a previously unidentified feature of local expression of the AMPA receptor.

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Citations

Apr 4, 2021·International Journal of Molecular Sciences·Yuyoung Joo, David R Benavides
Apr 4, 2021·International Journal of Molecular Sciences·Wanil KimKyung-Ha Lee

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Methods Mentioned

BETA
Assay
transfection
myristoylation
fluorescence recovery after photobleaching
pull down
PCR
transfections
immunoprecipitation
electrophoresis
chip

Software Mentioned

mfold
NIS
Fiji
ImageJ
FUJIFILM
Image Gauge
Elements

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