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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gangwani, L.
Right arrow Articles by Davis, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gangwani, L.
Right arrow Articles by Davis, R. J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, April 2005, p. 2744-2756, Vol. 25, No. 7
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.7.2744-2756.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

ZPR1 Is Essential for Survival and Is Required for Localization of the Survival Motor Neurons (SMN) Protein to Cajal Bodies{dagger}

Laxman Gangwani,1 Richard A. Flavell,2 and Roger J. Davis1,3*

Program in Molecular Medicine, University of Massachusetts Medical School,1 Howard Hughes Medical Institute, Worcester, Massachusetts,3 Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut2

Received 11 November 2004/ Returned for modification 10 December 2004/ Accepted 21 December 2004

Mutation of the survival motor neurons 1 (SMN1) gene causes motor neuron apoptosis and represents the major cause of spinal muscular atrophy in humans. Biochemical studies have established that the SMN protein plays an important role in spliceosomal small nuclear ribonucleoprotein (snRNP) biogenesis and that the SMN complex can interact with the zinc finger protein ZPR1. Here we report that targeted ablation of the Zpr1 gene in mice disrupts the subcellular localization of both SMN and spliceosomal snRNPs. Specifically, SMN localization to Cajal bodies and gems was not observed in cells derived from Zpr1–/– embryos and the amount of cytoplasmic snRNP detected in Zpr1–/– embryos was reduced compared with that in wild-type embryos. We found that Zpr1–/– mice die during early embryonic development, with reduced proliferation and increased apoptosis. These effects of Zpr1 gene disruption were confirmed and extended in studies of cultured motor neuron-like cells using small interfering RNA-mediated Zpr1 gene suppression; ZPR1 deficiency caused growth cone retraction, axonal defects, and apoptosis. Together, these data indicate that ZPR1 contributes to the regulation of SMN complexes and that it is essential for cell survival.

* Corresponding author. Mailing address: Program in Molecular Medicine, Howard Hughes Medical Institute, University of Massachusetts Medical School, 373 Plantation St., Worcester, MA 01605. Phone: (508) 856-6054. Fax: (508) 856-3210. E-mail: Roger.Davis{at}Umassmed.Edu.

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

Molecular and Cellular Biology, April 2005, p. 2744-2756, Vol. 25, No. 7
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.7.2744-2756.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Walker, M. P., Rajendra, T.K., Saieva, L., Fuentes, J. L., Pellizzoni, L., Matera, A. G. (2008). SMN complex localizes to the sarcomeric Z-disc and is a proteolytic target of calpain. Hum Mol Genet 17: 3399-3410 [Abstract] [Full Text]  
  • Wilson, M. D., Wang, D., Wagner, R., Breyssens, H., Gertsenstein, M., Lobe, C., Lu, X., Nagy, A., Burke, R. D., Koop, B. F., Howard, P. L. (2008). ARS2 Is a Conserved Eukaryotic Gene Essential for Early Mammalian Development. Mol. Cell. Biol. 28: 1503-1514 [Abstract] [Full Text]  
  • Mishra, A. K., Gangwani, L., Davis, R. J., Lambright, D. G. (2007). Structural insights into the interaction of the evolutionarily conserved ZPR1 domain tandem with eukaryotic EF1A, receptors, and SMN complexes. Proc. Natl. Acad. Sci. USA 104: 13930-13935 [Abstract] [Full Text]  
  • Ogawa, C., Usui, K., Aoki, M., Ito, F., Itoh, M., Kai, C., Kanamori-Katayama, M., Hayashizaki, Y., Suzuki, H. (2007). Gemin2 Plays an Important Role in Stabilizing the Survival of Motor Neuron Complex. J. Biol. Chem. 282: 11122-11134 [Abstract] [Full Text]  
  • Gangwani, L. (2006). Deficiency of the Zinc Finger Protein ZPR1 Causes Defects in Transcription and Cell Cycle Progression. J. Biol. Chem. 281: 40330-40340 [Abstract] [Full Text]  
  • Cioce, M., Boulon, S., Matera, A. G., Lamond, A. I. (2006). UV-induced fragmentation of Cajal bodies. JCB 175: 401-413 [Abstract] [Full Text]  
  • Doran, B., Gherbesi, N., Hendricks, G., Flavell, R. A., Davis, R. J., Gangwani, L. (2006). Deficiency of the zinc finger protein ZPR1 causes neurodegeneration. Proc. Natl. Acad. Sci. USA 103: 7471-7475 [Abstract] [Full Text]  
  • Renvoise, B., Khoobarry, K., Gendron, M.-C., Cibert, C., Viollet, L., Lefebvre, S. (2006). Distinct domains of the spinal muscular atrophy protein SMN are required for targeting to Cajal bodies in mammalian cells. J. Cell Sci. 119: 680-692 [Abstract] [Full Text]  


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