Drebrin Isoforms Critically Regulate NMDAR- and mGluR-Dependent LTD Induction

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Highly Sensitive and Quantitative Detection of Proteins and Their Isoforms by Capillary Isoelectric Focusing Method

Highly Sensitive and Quantitative Detection of Proteins and Their Isoforms by Capillary Isoelectric Focusing Method

Published on: September 19, 2018

Hiroki Yasuda^1,2,3, Nobuhiko Kojima^1,4, Kenji Hanamura¹

¹Department of Neurobiology and Behavior, Graduate School of Medicine, Gunma University, Maebashi, Japan.

Frontiers in Cellular Neuroscience

|October 24, 2018

Abstract:

Drebrin is an actin-binding protein that is preferentially expressed in the brain. It is highly localized in dendritic spines and regulates spine shapes. The embryonic-type (drebrin E) is expressed in the embryonic and early postnatal brain and is replaced by the adult-type (drebrin A) during development. In parallel, NMDA receptor (NMDAR)-dependent long-term depression (LTD) of synaptic transmission, induced by low-frequency stimulation (LFS), is dominant in the immature brain and decreases during development. Here, we report that drebrin regulates NMDAR-dependent and group 1 metabotropic glutamate receptor (mGluR)-dependent LTD induction in the hippocampus. While LFS induced NMDAR-dependent LTD in the developing hippocampus in wild-type (WT) mice, it did not induce LTD in developing drebrin E and A double knockout (DXKO) mice, indicating that drebrin is required for NMDAR-dependent LTD. On the other hand, LFS induced robust LTD dependent on mGluR5, one of group 1 mGluRs, in both developing and adult brains of drebrin A knockout (DAKO) mice, in which drebrin E is expressed throughout development and adulthood. Agonist-induced mGluR-dependent LTD was normal in WT and DXKO mice; however, it was enhanced in DAKO mice. Also, mGluR1, another group 1 mGluR, was involved in agonist-induced mGluR-dependent LTD in DAKO mice. These data suggest that abnormal drebrin E expression in adults promotes group 1 mGluR-dependent LTD induction. Therefore, while drebrin expression is critical for NMDAR-dependent LTD induction, developmental conversion from drebrin E to drebrin A prevents robust group 1 mGluR-dependent LTD.

Keywords:

NMDAR-dependent LTD development drebrin isoforms knockout mouse mGluR-dependent LTD

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