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

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

Research output: Contribution to journalArticle

108 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
DOIs
Publication statusPublished - 2000 Aug 15
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Reelin molecules assemble together to form a large protein complex, which is inhibited by the function-blocking CR-50 antibody'. Together they form a unique fingerprint.

  • Cite this