Fbxo45 forms a novel ubiquitin ligase complex and is required for neuronal development

Toru Saiga, Takaichi Fukuda, Masaki Matsumoto, Hirobumi Tada, Hirotaka James Okano, Hideyuki Okano, Keiichi I. Nakayama

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Fbxo45 is an F-box protein that is restricted to the nervous system. Unlike other F-box proteins, Fbxo45 was found not to form an SCF complex as a result of an amino acid substitution in the consensus sequence for Cul1 binding. Proteomics analysis revealed that Fbxo45 specifically associates with PAM (protein associated with Myc), a RING finger-type ubiquitin ligase. Mice deficient in Fbxo45 were generated and found to die soon after birth as a result of respiratory distress. Fbxo45-/- embryos show abnormal innervation of the diaphragm, impaired synapse formation at neuromuscular junctions, and aberrant development of axon fiber tracts in the brain. Similar defects are also observed in mice lacking Phr1 (mouse ortholog of PAM), suggesting that Fbxo45 and Phr1 function in the same pathway. In addition, neuronal migration was impaired in Fbxo45-/- mice. These results suggest that Fbxo45 forms a novel Fbxo45-PAM ubiquitin ligase complex that plays an important role in neural development.

Original languageEnglish
Pages (from-to)3529-3543
Number of pages15
JournalMolecular and cellular biology
Volume29
Issue number13
DOIs
Publication statusPublished - 2009 Jul

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Saiga, T., Fukuda, T., Matsumoto, M., Tada, H., Okano, H. J., Okano, H., & Nakayama, K. I. (2009). Fbxo45 forms a novel ubiquitin ligase complex and is required for neuronal development. Molecular and cellular biology, 29(13), 3529-3543. https://doi.org/10.1128/MCB.00364-09