2017.11.22

RNG105/caprin1, an RNA granule protein for dendritic mRNA localization, is essential for long-term memory formation

（Elife. 2017 Nov 21;6. pii: e29677. doi: 10.7554/eLife.29677.）

Nakayama K^1,2,3, Ohashi R^1,2, Shinoda Y^4,5, Yamazaki M⁶, Abe M⁶, Fujikawa A⁷, Shigenobu S^2,8, Futatsugi A⁹, Noda M^2,7, Mikoshiba K¹⁰, Furuichi T⁴, Sakimura K⁶, Shiina N^1,2,3.

¹Laboratory of Neuronal Cell Biology, National Institute for Basic Biology
²Department of Basic Biology, SOKENDAI
³Okazaki Institute for Integrative Bioscience
⁴Department of Applied Biological Science, Tokyo University of Science
⁵School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
⁶Department of Cellular Neurobiology, Brain Research Institute, Niigata University
⁷Division of Molecular Neurobiology, National Institute for Basic Biology
⁸Functional Genomics Facility, National Institute for Basic Biology
⁹Department of Basic Medical Science, Kobe City College of Nursing
¹⁰Laboratory for Developmental Neurobiology, Brain Science Institute

Abstract

Local regulation of synaptic efficacy is thought to be important for proper networking of neurons and memory formation. Dysregulation of global translation influences long-term memory in mice, but the relevance of the regulation specific for local translation by RNA granules remains elusive. Here, we demonstrate roles of RNG105/caprin1 in long-term memory formation. RNG105 deletion in mice impaired synaptic strength and structural plasticity in hippocampal neurons. Furthermore, RNG105-deficient mice displayed unprecedentedly severe defects in long-term memory formation in spatial and contextual learning tasks. Genome-wide profiling of mRNA distribution in the hippocampus revealed an underlying mechanism: RNG105 deficiency impaired the asymmetric somato-dendritic localization of mRNAs. Particularly, RNG105 deficiency reduced the dendritic localization of mRNAs encoding regulators of AMPAR surface expression, which was consistent with attenuated homeostatic AMPAR scaling in dendrites and reduced synaptic strength. Thus, RNG105 has an essential role, as a key regulator of dendritic mRNA localization, in long-term memory formation.

*Reprinted under a CC BY 4.0 license.

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