A cAMP/PKA-dependent synaptically targeted lncRNA mediates structural plasticity in hippocampal neurons by functionally interacting with the Spectrin/Ankyrin Network

Abstract

Activity-dependent structural plasticity at the synapse requires specific changes in the neuronal transcriptome. While much is known about the role of coding elements in this process, the role of the long-noncoding transcriptome remains elusive. Here we report the discovery of an intronic long noncoding RNA (lncRNA)--termed ADEPTR--whose expression is upregulated and is synaptically transported in a cAMP/PKA-dependent manner in hippocampal neurons, independent of its protein-coding host gene. Loss of ADEPTR function suppresses activity-dependent changes in synaptic transmission and structural plasticity of dendritic spines. Mechanistically, dendritic localization of ADEPTR is mediated by molecular motor protein Kif2A. ADEPTR physically binds to actin-scaffolding regulators Ankyrin (AnkB) and Spectrin (Sptn1) and is required for their dendritic localization. Taken together, this study demonstrates that ADEPTR regulates the dendritic Spectrin-Ankyrin network for structural plasticity at the synapse and illuminates a novel role for lncRNAs at the synapse. One Sentence SummaryWe have uncovered an intronic long noncoding RNA that is synaptically transported in a cAMP-dependent manner and is linked to cytoskeletal components of structural plasticity in hippocampal neurons.