title: Alternative splicing modulates subcellular localization of laforin.
abstract: Laforin is a dual-specificity phosphatase coded by the EPM2A gene defective in Lafora's progressive myoclonus epilepsy. We reported earlier that laforin is a cytoplasmic protein associated primarily with polyribosome. In the present study we characterized the expression of an EPM2A splice variant, named C-terISO, originating from the usage of a novel exon located in the 3'-untranslated region of exon 4 and encoding a laforin isoform containing unique sequences at its carboxyl terminus. Transfection studies demonstrate that, in addition to cytoplasm, the protein coded by C-terISO was targeted to the nucleus, a distinctive feature that was not observed for laforin coded by the major transcript of the EPM2A gene. The unique C-terminal sequence did not affect laforin's affinity for polysome, but sequestered nearly an equal amount of the protein into the nucleus. Our results are significant in light of the finding that laforin is an active phosphatase; therefore, isoforms targeted to different cellular compartments might dephosphorylate and regulate distinct cellular substrates.
authors.affiliation: Laboratory for Neurogenetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Ganesh
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamakawa
mesh_terms: D017398:Alternative Splicing; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D013347:Subcellular Fractions
chemical_list: D018076:DNA, Complementary; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C114990:EPM2A protein, human