Spastin subcellular localization is regulated through usage of different translation start sites and active export from the nucleus
| Autor: | Elena Riano, Pamela Claudiani, Gennaro Andolfi, Elena I. Rugarli, Alessia Errico |
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| Rok vydání: | 2005 |
| Předmět: |
Gene isoform
Cytoplasm Spastin Hereditary spastic paraplegia Active Transport Cell Nucleus Codon Initiator Biology Microtubule Chlorocebus aethiops medicine Animals Humans Protein Isoforms Nuclear export signal Adenosine Triphosphatases Cell Nucleus Calcium-Binding Proteins Cell Biology medicine.disease Subcellular localization Protein Structure Tertiary Cell biology Cell nucleus medicine.anatomical_structure Biochemistry Protein Biosynthesis COS Cells Nuclear transport 5' Untranslated Regions HeLa Cells |
| Zdroj: | Experimental Cell Research. 309:358-369 |
| ISSN: | 0014-4827 |
| DOI: | 10.1016/j.yexcr.2005.06.009 |
| Popis: | Most cases of autosomal-dominant hereditary spastic paraplegia are linked to mutations in SPG4 encoding spastin, a protein involved in microtubule dynamics and membrane trafficking. In pyramidal neurons of the motor cortex and in immortalized motor neurons, spastin is localized to the synaptic terminals and growth cones. However, in other neurons and in proliferating cells spastin is prevalently nuclear. The mechanisms that determine targeting of spastin to the nucleus or the cytoplasm are unknown. We show here that the SPG4 mRNA is able to direct synthesis of two spastin isoforms, 68 and 60 kDa, respectively, through usage of two different translational start sites. Both isoforms are imported into the nucleus, but the 68-kDa isoform contains two nuclear export signals that efficiently drive export to the cytoplasm. Nuclear export is leptomycin-B sensitive. The cytoplasmic 68-kDa spastin isoform is more abundant in the brain and the spinal cord than in other tissues. Our data indicate that spastin function is modulated through usage of alternative translational start sites and active nuclear import and export, and open new perspectives for the pathogenesis of hereditary spastic paraplegia. |
| Databáze: | OpenAIRE |
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