TY - JOUR
T1 - miR-501-3p mediates the activity-dependent regulation of the expression of AMPA receptor subunit GluA1
AU - Hu, Zhonghua
AU - Zhao, Jun
AU - Hu, Tianyi
AU - Luo, Yan
AU - Zhu, Jun
AU - Li, Zheng
PY - 2015
Y1 - 2015
N2 - The number of α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid receptors (AMPARs) in synapses determines synaptic strength. AMPAR expression can be regulated locally in dendrites by synaptic activity. The mechanisms of activity-dependent local regulation of AMPAR expression, however, remain unclear. Here, we tested whether microRNAs (miRNAs) are involved in N-methyl-d-aspartate (NMDA) receptor (NMDAR)- dependent AMPAR expression. We used the 3' untranslated region of Gria1, which encodes the AMPA receptor subunit GluA1, to pull down miRNAs binding to it and analyzed these miRNAs using next-generation deep sequencing. Among the identified miRNAs, miR-501-3p is also a computationally predicted Gria1-targeting miRNA. We confirmed that miR-501-3p targets Gria1 and regulates its expression under physiological conditions. The expression of miR-501-3p and GluA1, moreover, is inversely correlated during postnatal brain development. miR-501-3p expression is up-regulated locally in dendrites through the NMDAR subunit GluN2A, and this regulation is required for NMDA-induced suppression of GluA1 expression and long-lasting remodeling of dendritic spines. These findings elucidate a miRNA-mediated mechanism for activity-dependent, local regulation of AMPAR expression in dendrites.
AB - The number of α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid receptors (AMPARs) in synapses determines synaptic strength. AMPAR expression can be regulated locally in dendrites by synaptic activity. The mechanisms of activity-dependent local regulation of AMPAR expression, however, remain unclear. Here, we tested whether microRNAs (miRNAs) are involved in N-methyl-d-aspartate (NMDA) receptor (NMDAR)- dependent AMPAR expression. We used the 3' untranslated region of Gria1, which encodes the AMPA receptor subunit GluA1, to pull down miRNAs binding to it and analyzed these miRNAs using next-generation deep sequencing. Among the identified miRNAs, miR-501-3p is also a computationally predicted Gria1-targeting miRNA. We confirmed that miR-501-3p targets Gria1 and regulates its expression under physiological conditions. The expression of miR-501-3p and GluA1, moreover, is inversely correlated during postnatal brain development. miR-501-3p expression is up-regulated locally in dendrites through the NMDAR subunit GluN2A, and this regulation is required for NMDA-induced suppression of GluA1 expression and long-lasting remodeling of dendritic spines. These findings elucidate a miRNA-mediated mechanism for activity-dependent, local regulation of AMPAR expression in dendrites.
UR - http://www.scopus.com/inward/record.url?scp=84928261537&partnerID=8YFLogxK
U2 - 10.1083/jcb.201404092
DO - 10.1083/jcb.201404092
M3 - Article
C2 - 25800054
AN - SCOPUS:84928261537
SN - 0021-9525
VL - 208
SP - 949
EP - 959
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 7
ER -