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Spinal muscular atrophy disrupts the interaction of ZPR1 with the SMN protein

Nature Cell Biology volume 3, pages 376–383 (2001)Cite this article

Abstract

The survival motor neurons (smn) gene in mice is essential for embryonic viability. In humans, mutation of the telomeric copy of the SMN1 gene causes spinal muscular atrophy, an autosomal recessive disease. Here we report that the SMN protein interacts with the zinc-finger protein ZPR1 and that these proteins colocalize in small subnuclear structures, including gems and Cajal bodies. SMN and ZPR1 redistribute from the cytoplasm to the nucleus in response to serum. This process is disrupted in cells from patients with Werdnig–Hoffman syndrome (spinal muscular atrophy type I) that have SMN1 mutations. Similarly, decreased ZPR1 expression prevents SMN localization to nuclear bodies. Our data show that ZPR1 is required for the localization of SMN in nuclear bodies.

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Figure 1: Interaction of endogenous ZPR1 with SMN.
Figure 2: Interaction of ZPR1 and SMN requires the C-terminal region of both proteins.
Figure 3: Colocalization of nuclear ZPR1 with SMN.
Figure 4: Effect of ZPR1 on in vitro pre-mRNA splicing.
Figure 5: Interaction of ZPR1 with SMN is disrupted in cells derived from SMA patients.
Figure 6: ZPR1 and SMN are required for localization in nuclear gems.

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Acknowledgements

We thank E. K. L. Chan and G. Dreyfuss for providing reagents, and K. Gemme for administrative assistance. This study was supported by a grant from the National Cancer Institute. R.J.D. is an investigator of the Howard Hughes Medical Institute.

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Author notes

  1. Manoj Sharma

    Present address: Strategic BioSolutions Inc., 128 Sandy Drive, Newark, Delaware, 19713, USA

Authors and Affiliations

  1. Program in Molecular Medicine, University of Massachussetts Medical School, 373 Plantation St, Worcester, 01605, Massachussetts, USA

    Laxman Gangwani, Monique Mikrut, Manoj Sharma & Roger J. Davis

  2. Department of Biochemistry & Molecular Biology, University of Massachussetts Medical School, 373 Plantation St, Worcester, 01605, Massachussetts, USA

    Laxman Gangwani, Monique Mikrut, Manoj Sharma & Roger J. Davis

  3. Department of Biology, Assumption College, 500 Salisbury St, Worcester, 01615, Massachusetts, USA

    Steven Theroux

  4. Howard Hughes Medical Institute, 373 Plantation Street, Worcester, 01605, Massachusetts, USA

    Roger J. Davis

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Correspondence to Roger J. Davis.

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Gangwani, L., Mikrut, M., Theroux, S. et al. Spinal muscular atrophy disrupts the interaction of ZPR1 with the SMN protein. Nat Cell Biol 3, 376–383 (2001). https://doi.org/10.1038/35070059

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