Practice question

Directionality of nucleocytoplasmic transport relies on asymmetric distribution of small GTPase Ran nucleotide states forming gradient across nuclear envelope. Regulator RCC1 RanGEF bound to chromatin generates high Ran-GTP concentration inside nucleus through exchange of GDP for GTP, while cytoplasmic filaments of nuclear pore complex associated with RanGAP and RanBP1 stimulate GTP hydrolysis to Ran-GDP in cytosol, depleting Ran-GTP outside. Importin alpha/beta-cargo complexes formed in cytoplasm traverse pore via interactions with FG nucleoporins, encountering Ran-GTP in nucleus which binds importin beta causing conformational change releasing cargo into nucleoplasm. Conversely exportin CRM1 binds cargo containing leucine-rich nuclear export signal only cooperatively with Ran-GTP forming ternary export complex in nucleus that moves to cytoplasm where GTP hydrolysis after RanGAP action dissociates complex and releases cargo. This gradient ensures accumulation of nuclear proteins such as histones and transcription factors in nucleus and cytoplasmic proteins outside, while also regulating spindle assembly during mitosis and nuclear envelope reformation.