TY - JOUR TI - The E3 ubiquitin ligase IDOL regulates synaptic ApoER2 levels and is important for plasticity and learning AU - Gao, Jie AU - Marosi, Mate AU - Choi, Jinkuk AU - Achiro, Jennifer M AU - Kim, Sangmok AU - Li, Sandy AU - Otis, Klara AU - Martin, Kelsey C AU - Portera-Cailliau, Carlos AU - Tontonoz, Peter A2 - Kim, Eunjoon VL - 6 PY - 2017 DA - 2017/09/11 SP - e29178 C1 - eLife 2017;6:e29178 DO - 10.7554/eLife.29178 UR - https://doi.org/10.7554/eLife.29178 AB - 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. KW - lipoprotein receptor KW - ApoE KW - dendritic spines KW - ubiquitin ligase JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -