The extremely conserved C-terminal region of Reelin is not necessary for secretion but is required for efficient activation of downstream signaling

Yoshimi Nakano, Takao Kohno, Terumasa Hibi, Shiori Kohno, Atsushi Baba, Katsuhiko Mikoshiba, Kazunori Nakajima, Mitsuharu Hattori

研究成果: Article査読

62 被引用数 (Scopus)

抄録

Reelin is a very large secreted glycoprotein essential for correct development of the mammalian brain. It is also implicated in higher functions and diseases of human brain. However, whether or not secretion of Reelin is regulated and how Reelin transmits signals remain largely unknown. Reelin protein is composed of an N-terminal F-spondin-like domain, Reelin repeats, and a short and highly basic C-terminal region (CTR). The primary sequence of CTR is almost completely conserved among vertebrates except fishes, indicating its importance. A prevailing idea regarding the function of CTR is that it is required for the secretion of Reelin, although this remains unproven. Here we aimed to clarify the function of Reelin CTR. Neither deleting most of CTR nor replacing CTR with unrelated amino acids affected secretion efficiency, indicating that CTR is not absolutely required for the secretion of Reelin. We also found that Reelin mutants without CTR were less potent in activating the downstream signaling in cortical neurons. Although these mutants were able to bind to the Reelin receptor ectodomain as efficiently as wild-type Reelin, quite interestingly, their ability to bind to the isolated cell membrane bearing Reelin receptors or receptor-expressing cells (including cortical neurons) was much weaker than that of wild-type Reelin. Therefore, it is concluded that the CTR of Reelin is not essential for its secretion but is required for efficient activation of downstream signaling events, presumably via binding to an unidentified "coreceptor" molecule(s) on the cell membrane.

本文言語English
ページ(範囲)20544-20552
ページ数9
ジャーナルJournal of Biological Chemistry
282
28
DOI
出版ステータスPublished - 2007 7月 13

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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