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lncRNA ADEPTR的活性调节突触靶向通过将Sptn1和AnkB定位于树突中来介导结构可塑性。

Activity-regulated synaptic targeting of lncRNA ADEPTR mediates structural plasticity by localizing Sptn1 and AnkB in dendrites.

作者信息

Grinman Eddie, Nakahata Yoshihisa, Avchalumov Yosef, Espadas Isabel, Swarnkar Supriya, Yasuda Ryohei, Puthanveettil Sathyanarayanan V

机构信息

Department of Neuroscience, Scripps Research, 130 Scripps Way, Jupiter, FL 33458, USA.

Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA.

出版信息

Sci Adv. 2021 Apr 16;7(16). doi: 10.1126/sciadv.abf0605. Print 2021 Apr.

DOI:10.1126/sciadv.abf0605
PMID:33863727
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8051873/
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-that is up-regulated and synaptically transported in a cAMP/PKA-dependent manner in hippocampal neurons, independently 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) via a conserved sequence and is required for their dendritic localization. Together, this study demonstrates how activity-dependent synaptic targeting of an lncRNA mediates structural plasticity at the synapse.

摘要

突触处依赖活动的结构可塑性需要神经元转录组发生特定变化。虽然我们对编码元件在这一过程中的作用了解很多，但长链非编码转录组的作用仍不清楚。在这里，我们报告发现了一种内含子长链非编码RNA（lncRNA）——称为ADEPTR——它在海马神经元中以cAMP/PKA依赖的方式上调并通过突触运输，与其蛋白质编码宿主基因无关。ADEPTR功能的丧失会抑制突触传递中依赖活动的变化以及树突棘的结构可塑性。从机制上讲，ADEPTR的树突定位由分子运动蛋白Kif2A介导。ADEPTR通过一个保守序列与肌动蛋白支架调节剂锚蛋白（AnkB）和血影蛋白（Sptn1）物理结合，并且是它们树突定位所必需的。总之，这项研究证明了lncRNA的活动依赖性突触靶向如何介导突触处的结构可塑性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08e5/8051873/81de094b4a9b/abf0605-F7.jpg
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