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The survival motor neurons protein uses its ZPR for nuclear localization

Nature Cell Biology volume 3, pages E93–E94 (2001)Cite this article

Spinal muscular atrophy is caused by mutations in the survival motor neurons gene, SMN1. The SMN protein localizes to both the cytoplasm and the nuclear bodies. One hallmark of spinal muscular atrophy is the failure of SMN to localize within these nuclear bodies. A recent study has identified a protein called ZPR1 that is required for nuclear translocation of SMN.

Spinal muscular atrophy (SMA) is a neurodegenerative disorder resulting in apoptosis of motor neurons in the anterior horn of the spinal cord, progressive paralysis in the limbs and trunk, followed by muscular atrophy and infant death1. SMA is characterized by an autosomal recessive inheritance pattern and, with a carrier frequency of about 1 in 50, it is the most common genetic cause of childhood mortality. More than 95% of cases of SMA are due to mutations in the survival motor neurons locus2, which encompasses at least two genes—SMN1 and SMN2. Most SMA-causing mutations result in the expression of a truncated form of the protein3 that lacks sequences encoded by exon 7 (SMNΔex7). In fact, Cre-mediated homozygous deletion of exon 7 in mouse neurons is lethal and reveals a defect in the nuclear targeting of the SMNΔex7 isoform4. In this issue of Nature Cell Biology, Davis and colleagues9 reveal that the zinc finger protein ZPR1 is required for the accumulation of SMN in nuclear bodies (on page 376 ). Taken together with previous results from their laboratory, these data outline the existence of a potential signalling pathway connecting cellular proliferation signals such as epidermal growth factor (EGF) with the machinery responsible for the biogenesis of small nuclear ribonucleoprotein (snRNP) particles and pre-mRNA splicing.

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Figure 1: Model of ZPR1 interaction with SMN.

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  1. Department of Genetics, Center for Human Genetics and Program in Cell Biology Case Western Reserve University and University Hospitals of Cleveland, Cleveland, 44106-4955, OH, USA

    A. Gregory Matera & Michael D. Hebert

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  1. A. Gregory Matera
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  2. Michael D. Hebert
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Matera, A., Hebert, M. The survival motor neurons protein uses its ZPR for nuclear localization . Nat Cell Biol 3, E93–E94 (2001). https://doi.org/10.1038/35070157

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