Reelin molecules assemble together to form a large protein complex, which is inhibited by the function-blocking CR-50 antibody

Naoko Utsunomiya-Tate, Kenichiro Kubo, Shin Ichi Tate, Masatsune Kainosho, Eisaku Katayama, Kazunori Nakajima, Katsuhiko Mikoshiba

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Reelin is a key mediator of ordered neuronal alignment in the brain. Here, we demonstrate that Reelin molecules assemble with each other to form a huge protein complex both in vitro and in vivo. The Reelin-Reelin interaction clearly is inhibited by the function-blocking anti-Reelin antibody, CR-50, at a concentration known to inhibit Reelin function. This assembly is mediated by electrostatic interaction of the CR-50 epitope region. Recombinant CR-50 epitope fragments spontaneously constitute a soluble, string-like homopolymer with a regularly repeated structure composed of more than 40 monomers. Mutated Reelin, which lacks the CR-50 epitope region, cannot form a homopolymer and fails to induce efficient tyrosine phosphorylation of Disabled 1 (Dab1), which should occur to transduce the Reelin signal. These data suggest that Reelin exerts its biological function by composing a large protein assembly driven by the CR-50 epitope region, proposing a novel model of the Reelin signaling in neurodevelopment.

Original languageEnglish
Pages (from-to)9729-9734
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number17
Publication statusPublished - 2000 Aug 15
Externally publishedYes

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Epitopes
Antibodies
Proteins
Blocking Antibodies
Static Electricity
Tyrosine
Anti-Idiotypic Antibodies
Phosphorylation
Brain

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Reelin molecules assemble together to form a large protein complex, which is inhibited by the function-blocking CR-50 antibody. / Utsunomiya-Tate, Naoko; Kubo, Kenichiro; Tate, Shin Ichi; Kainosho, Masatsune; Katayama, Eisaku; Nakajima, Kazunori; Mikoshiba, Katsuhiko.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 17, 15.08.2000, p. 9729-9734.

Research output: Contribution to journalArticle

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