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Title: Spastin subcellular localization is regulated through usage of different translation start sites and active export from the nucleus

Abstract

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.

Authors:
 [1];  [1];  [1];  [1];  [2]
  1. Telethon Institute of Genetics and Medicine (TIGEM), via P. Castellino 111, 80131 Naples (Italy)
  2. Telethon Institute of Genetics and Medicine (TIGEM), via P. Castellino 111, 80131 Naples, (Italy)
Publication Date:
OSTI Identifier:
20717661
Resource Type:
Journal Article
Journal Name:
Experimental Cell Research
Additional Journal Information:
Journal Volume: 309; Journal Issue: 2; Other Information: DOI: 10.1016/j.yexcr.2005.06.009; PII: S0014-4827(05)00278-8; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0014-4827
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BRAIN; CYTOPLASM; GROWTH; MEMBRANES; MICROTUBULES; MUTATIONS; NERVE CELLS; PATHOGENESIS; PROTEINS; RABBIT TUBES; SPINAL CORD; SYNTHESIS

Citation Formats

Claudiani, Pamela, Riano, Elena, Errico, Alessia, Andolfi, Gennaro, and Rugarli, Elena I. Spastin subcellular localization is regulated through usage of different translation start sites and active export from the nucleus. United States: N. p., 2005. Web. doi:10.1016/j.yexcr.2005.06.009.
Claudiani, Pamela, Riano, Elena, Errico, Alessia, Andolfi, Gennaro, & Rugarli, Elena I. Spastin subcellular localization is regulated through usage of different translation start sites and active export from the nucleus. United States. https://doi.org/10.1016/j.yexcr.2005.06.009
Claudiani, Pamela, Riano, Elena, Errico, Alessia, Andolfi, Gennaro, and Rugarli, Elena I. 2005. "Spastin subcellular localization is regulated through usage of different translation start sites and active export from the nucleus". United States. https://doi.org/10.1016/j.yexcr.2005.06.009.
@article{osti_20717661,
title = {Spastin subcellular localization is regulated through usage of different translation start sites and active export from the nucleus},
author = {Claudiani, Pamela and Riano, Elena and Errico, Alessia and Andolfi, Gennaro and Rugarli, Elena I},
abstractNote = {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.},
doi = {10.1016/j.yexcr.2005.06.009},
url = {https://www.osti.gov/biblio/20717661}, journal = {Experimental Cell Research},
issn = {0014-4827},
number = 2,
volume = 309,
place = {United States},
year = {Sat Oct 01 00:00:00 EDT 2005},
month = {Sat Oct 01 00:00:00 EDT 2005}
}