Fig. 2

Ranbp1: function, craniofacial and neural phenotypes. a In the nucleus, the exportin (Xpo1) binds the cargo tagged with nuclear export signals (NES) and Ran-GTP and diffuses through the pore to the cytoplasm. Once in the cytoplasm, Ranbp1 along with RanGAPs that hydrolyze Ran-GTP into Ran-GDP dissociate the complex and release the transported macromolecule. In the cytoplasm, importin-α/β heterodimer forms a complex with cytoplasmic cargos tagged with a nuclear localization sequence (NLS) and Ran-GDP and transports them into the nucleus. Inside the nucleus, the high concentration of Ran-GTP rapidly binds to importin-β to dissociate the complex, releasing the transported cargos, followed by recycling of the importins back to the cytoplasm. RCC (a guanine nucleotide exchange factor) stimulates Ran-GDP to release its GDP and pick up GTP [164]. b, c Examination of E17.5 embryos shows that Ranbp1^−/− embryos have visible abnormalities including a smaller and shorter head with a narrower face. d Coronal sections show a distinctive smaller, thinner cortex in E15.5 Ranbp1^−/− embryos. e Layer 2/3 projection neurons, labeled for Cux1, are disrupted in E17.5 Ranbp1^−/− cortex [170]. Cux1 and Ctip2 labels subsets of upper- and lower-layer projection neurons, respectively. Scale bars: b = 250 μm, c = 100 μm, d = 25 μm, e = 50 μm