The E3 ubiquitin ligase IDOL regulates synaptic ApoER2 levels and is important for plasticity and learning
Year: 2017
Type: article
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.
Source: eLife
DOI: 10.7554/elife.29178
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: New Molecules in Triglyceride Metabolism and Adipogenesis, The Idol-ApoE receptor pathway in Alzheimer's disease, Synapse to Nuclear Signaling During Long-Lasting Neuronal Plasticity, Nuclear Receptor Signaling Pathways in Atherogenesis, Mechanisms of structural neuronal plasticity and functional remapping after strok, G9000019033
OpenAlex ID: W2754402377