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Elife. 2017 Sep 11;6. pii: e29178. doi: 10.7554/eLife.29178.

The E3 ubiquitin ligase IDOL regulates synaptic ApoER2 levels and is important for plasticity and learning.

Author information

1
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, United States.
2
Departments of Neurology and Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, United States.
3
Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, United States.
4
Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, United States.
5
Howard Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, United States.
#
Contributed equally

Abstract

Neuronal ApoE receptors are linked to learning and memory, but the pathways governing their abundance, and the mechanisms by which they affect the function of neural circuits are incompletely understood. Here we demonstrate that the E3 ubiquitin ligase IDOL determines synaptic ApoER2 protein levels in response to neuronal activation and regulates dendritic spine morphogenesis and plasticity. IDOL-dependent changes in ApoER2 abundance modulate dendritic filopodia initiation and synapse maturation. Loss of IDOL in neurons results in constitutive overexpression of ApoER2 and is associated with impaired activity-dependent structural remodeling of spines and defective LTP in primary neuron cultures and hippocampal slices. IDOL-deficient mice show profound impairment in experience-dependent reorganization of synaptic circuits in the barrel cortex, as well as diminished spatial and associative learning. These results identify control of lipoprotein receptor abundance by IDOL as a post-transcriptional mechanism underlying the structural and functional plasticity of synapses and neural circuits.

KEYWORDS:

ApoE; cell biology; dendritic spines; lipoprotein receptor; mouse; neuroscience; ubiquitin ligase

PMID:
28891791
PMCID:
PMC5593505
DOI:
10.7554/eLife.29178
[Indexed for MEDLINE]
Free PMC Article

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