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. 2017 May 1;10(5):559–579. doi: 10.1242/dmm.027730

Fig. 4.

Fig. 4.

Subcellular mislocalization of partners and substrates of Ranbp2 in motoneurons of SLICK-H::Ranbp2flox/flox mice. (A) Schematic diagram of Ranbp2, its domains and partners thereof. Numbering refers to residues in primary sequence of Ranbp2. Domains are not drawn to scale. (B) Exportin 1 (c,h) is prominently localized at the nuclear rim and excluded from the nucleolus of +/+, whereas there complete loss of nuclear rim staining by exportin 1 and its subcellular distribution becomes highly diffused across all subcellular compartments of YFP+ motoneurons of −/− mice. Ran GTPase distribution (d,i) changes from a predominantly cytosolic localization in +/+ to highly diffuse across all subcellular compartments of −/− mice. Ran GTPase localization at the nuclear rim is also strongly decreased among YFP+ motoneurons of −/− mice. (C) Importin β (c,h) is prominently localized at the nuclear rim of +/+, whereas its localization at the nuclear rim is strongly decreased among YFP+ motoneurons of −/− mice. There is also prominent intranuclear sequestration of importin β in YFP+ motoneurons of −/− mice. Ran-GTP localization (d,i) at the nuclear rim is lost among all YFP+ motoneurons of −/− mice. (D) HDAC4 subcellular localization (c,g) is drastically changed in −/− mice. HDAC4 is found exclusively in the cytoplasm compartment of all YFP+ motoneurons of +/+, but this subcellular partitioning or its expression is lost in YFP+ motoneurons of −/− mice. (B-D) Representative images of motoneurons at d10 (day10) post-tamoxifen administration. Scale bars: 25 µm. Graphs on the right in B-D are quantitation analyses of nuclear rim (NR) staining for exportin 1, importin β, Ran GTPase and Ran-GTP, and exclusive cytosolic (Cyt) localization of HDAC4 in YFP+ motoneurons of +/+ and −/− mice. Data are expressed as mean±s.d.; n=3 or 4 mice/genotype; Student's t-tests. LD, leucine-rich domain; RBDn=1–4, Ran GTPase-binding domains, n=1-4; ZnFn=7, zinc finger-rich domains; KBD, kinesin 1-binding domain; CLD, cyclophilin-like domain; IR1 and IR2, internal repeats 1 and 2, respectively; M, middle domain between IR1 and IR2; O, overlapping region between CLD and IR1; CY, cyclophilin domain; Exp1, exportin 1; impβ, importin β; HDAC4, histone deacetylase 4; Ran, Ran GTPase; 26S, subunits of the 26S proteasome; −/−, SLICK-H::Ranbp2flox/flox; +/+, SLICK-H::Ranbp2+/+.