This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Saiga, T.
Right arrow Articles by Nakayama, K. I.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Saiga, T.
Right arrow Articles by Nakayama, K. I.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2009, p. 3529-3543, Vol. 29, No. 13
0270-7306/09/$08.00+0     doi:10.1128/MCB.00364-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Fbxo45 Forms a Novel Ubiquitin Ligase Complex and Is Required for Neuronal Development{triangledown} ,{dagger}

Toru Saiga,1,2 Takaichi Fukuda,3 Masaki Matsumoto,1,2 Hirobumi Tada,4,5 Hirotaka James Okano,5 Hideyuki Okano,5 and Keiichi I. Nakayama1,2*

Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan,1 CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan,2 Department of Anatomy and Neurobiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan,3 Physiology and Neuroendocrinology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan,4 Department of Physiology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan5

Received 20 March 2009/ Accepted 17 April 2009

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.

* Corresponding author. Mailing address: Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan. Phone: 81-92-642-6815. Fax: 81-92-642-6819. E-mail: nakayak1{at}bioreg.kyushu-u.ac.jp

{triangledown} Published ahead of print on 27 April 2009.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, July 2009, p. 3529-3543, Vol. 29, No. 13
0270-7306/09/$08.00+0     doi:10.1128/MCB.00364-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»