Secreted Reelin molecules form homodimers

Kenichiro Kubo, Katsuhiko Mikoshiba, Kazunori Nakajima

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

During mammalian brain development, neurons are generated along the ventricle, migrate radially, and become aligned in defined patterns. These precise patterns of neuronal alignment are regulated by an extracellular matrix protein Reelin, and binding of Reelin to its receptors induces tyrosine phosphorylation of the intracellular adaptor protein disabled 1 (Dab1). We recently reported that Reelin molecules assemble to form a homomeric protein complex. Although the number of molecules in the full-length complex is unknown, recombinant N-terminal fragments, which contain the epitope for the function-blocking CR-50 antibody, assembled to form a complex of more than 40 monomers. When the N-terminus was deleted from Reelin, the truncated protein did not form a stable complex. To further characterize the Reelin assembly, we performed biochemical analysis of the full-length Reelin assembly in this study. Here, we report that a full-length Reelin forms a disulfide-linked homodimer. A chemical crosslinking experiment on secreted Reelin confirmed that only dimers are formed by the full-length protein. However, interestingly, chemical crosslinking of the N-terminus-truncated Reelin resulted in the formation of larger complexes, in addition to dimers, suggesting that the tertiary structure required for the proper and stable assembly/dimerization was altered by the truncation. The truncated protein did not induce efficient tyrosine phosphorylation of Dab1, although it bound well to the receptors. These findings demonstrate the functional importance of the N-terminal region of Reelin for proper dimerization and signaling. Proper but not simple extracellular crosslinking of the receptors by these dimers may be important for Reelin signaling to occur.

Original languageEnglish
Pages (from-to)381-388
Number of pages8
JournalNeuroscience Research
Volume43
Issue number4
DOIs
Publication statusPublished - 2002
Externally publishedYes

Fingerprint

Dimerization
Proteins
Phosphorylation
Extracellular Matrix Proteins
Protein Binding
Disulfides
Tyrosine
Epitopes
Neurons
Antibodies
Brain
tyrosine receptor
reelin protein

Keywords

  • Cortical development
  • Dimer
  • Disabled 1
  • Neuronal migration
  • Reeler
  • Reelin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Secreted Reelin molecules form homodimers. / Kubo, Kenichiro; Mikoshiba, Katsuhiko; Nakajima, Kazunori.

In: Neuroscience Research, Vol. 43, No. 4, 2002, p. 381-388.

Research output: Contribution to journalArticle

Kubo, Kenichiro ; Mikoshiba, Katsuhiko ; Nakajima, Kazunori. / Secreted Reelin molecules form homodimers. In: Neuroscience Research. 2002 ; Vol. 43, No. 4. pp. 381-388.
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