Extended Data Figure 4. Nuclear import and export is altered by G₄C₂-58 expression.

a, A threonine to asparagine substitution at residue 24 in the Ran protein abolishes the affinity for GTP and reduces its affinity for GDP. Hence, the Ran (T24N) is always in either a nucleotide free state or in its inactive, GDP-bound state, and acts as dominant negative. RANT24N expression driven by GMR-GAL4 causes a mild eye phenotype when expressed in the absence of G₄C₂-58 (upper row, right panel). The G₄C₂-58 rough eye phenotype is strongly enhanced by dominant negative RANT24N expression (middle row, left panel). The G₄C₂-58 eye phenotype is significantly enhanced by knockdown of Nup153 by two independent RNAi lines (middle row, two right panels). The G₄C₂-58 eye phenotype is also mildly enhanced by knockdown of transportin (Trn) (bottom row). b, Knockdown of Crm1 in flies expressing G₄C₂-58 induces a mild enhancement of the G₄C₂-58 eye phenotype (left vs. middle). Crm1 knockdown in the absence of G₄C₂-58 repeats does not produce a rough eye phenotype (left). c, Expression of two copies of G₄C₂-58 in the Drosophila motor neurons leads to reduced viability (50%). Chemical inhibition of Crm1 with Leptomycin B (500 nM) enhances G₄C₂-58 toxicity resulting in reduced viability (23%). Leptomycin B does not impede viability (100%) in Drosophila expressing GFP.