Down-Regulation of miRNA-708 Promotes Aberrant Calcium Signaling by Targeting Neuronatin in a Mouse Model of Angelman Syndrome

Frontiers in Molecular Neuroscience
Naman VatsaNihar Ranjan Jana

Abstract

The expression of ubiquitin ligase UBE3A is paternally imprinted in neurons and loss of function of maternally inherited UBE3A causes Angelman syndrome (AS), a neurodevelopmental disorder characterized by severe intellectual disability and motor disturbances. Over activation of UBE3A is also linked with autism. Mice deficient for maternal Ube3a (AS mice) exhibit various behavioral features of AS including cognitive and motor deficits although the underlying molecular mechanism is poorly understood. Here, we investigated possible involvement of miRNA in AS pathogenesis and identified miR-708 as one of the down-regulated miRNA in the brain of AS mice. This miR-708 targets endoplasmic reticulum resident protein neuronatin (a developmentally regulated protein in the brain) leading to decrease in intracellular Ca2+. Suppression of miR-708 or ectopic expression of neuronatin increased the level of intracellular Ca2+ and phosphorylation of CaMKIIα at Thr286. Neuronatin level was significantly increased in various brain regions of AS mice during embryonic and early postnatal days as well as in parvalbumin-positive GABAergic neurons during adulthood with respect to age-matched wild type controls. Differentiated cultured primary cortical...Continue Reading

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Citations

Oct 19, 2019·Brain Sciences·Giovanni SchepiciEmanuela Mazzon
Feb 23, 2020·The FEBS Journal·Carina MarangaSimão Teixeira da Rocha
Aug 21, 2020·Learning & Memory·Maria N Schultz, Jacqueline N Crawley

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Methods Mentioned

BETA
ubiquitination
genotyping
transfection
PCR

Software Mentioned

NIH Image
iLife Discoveries
NIS elements AR
Expression Consoles
DIANA
microT
Affymatrix Expression Console
TargetScan
GeneSpring GX
Affymetrix Expression Console

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