Reelin-Nrp1 interaction regulates neocortical dendrite development in a context-specific manner

Takao Kohno, Keisuke Ishii, Yuki Hirota, Takao Honda, Makoto Makino, Takahiko Kawasaki, Kazunori Nakajima, Mitsuharu Hattori

研究成果: Article査読

抄録

Reelin plays versatile roles in neocortical development. The C-terminal region (CTR) of Reelin is required for the correct formation of the superficial structure of the neocortex; however, the mechanisms by which this position-specific effect occurs remain largely unknown. In this study, we demonstrate that Reelin with an intact CTR binds to neuropilin-1 (Nrp1), a transmembrane protein. Both male and female mice were used. Nrp1 is localized with very-low-density lipoprotein receptor (VLDLR), a canonical Reelin receptor, in the superficial layers of the developing neocortex. It forms a complex with VLDLR, and this interaction is modulated by the alternative splicing of VLDLR. Reelin with an intact CTR binds more strongly to the VLDLR/Nrp1 complex than to VLDLR alone. Knockdown of Nrp1 in neurons leads to the accumulation of Dab1 protein. Since the degradation of Dab1 is induced by Reelin signaling, it is suggested that Nrp1 augments Reelin signaling. The interaction between Reelin and Nrp1 is required for normal dendritic development in superficial-layer neurons. All of these characteristics of Reelin are abrogated by proteolytic processing of the six C-terminal amino acid residues of Reelin (0.17% of the whole protein). Therefore, Nrp1 is a coreceptor molecule for Reelin and, together with the proteolytic processing of Reelin, can account for context-specific Reelin function in brain development.

本文言語English
ページ(範囲)8248-8261
ページ数14
ジャーナルJournal of Neuroscience
40
43
DOI
出版ステータスPublished - 2020 10 21

ASJC Scopus subject areas

  • Neuroscience(all)

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