The export of proteins from the nucleus requires:
Export of proteins from the nucleus depends on recognition of leucine-rich nuclear export signals that provide dominant cue for exit to the cytoplasm. Canonical NES consists of short amphipathic alpha-helix with regularly spaced large hydrophobic residues, typically leucine, isoleucine, valine or phenylalanine, arranged in pattern Φ-X2-3-Φ-X2-3-Φ-X-Φ where Φ denotes hydrophobic. This motif docks into hydrophobic groove formed by HEAT repeats 11 and 12 of chromosome region maintenance 1, CRM1, also called Exportin-1 or XPO1, stabilized only when Ran is in GTP-bound state present at high concentration in nucleoplasm due to chromatin-bound RCC1 guanine exchange factor. Formation of trimeric cargo-CRM1-RanGTP complex enables translocation through FG nucleoporins via transient hydrophobic interactions. On cytoplasmic side, RanGAP1 anchored to RanBP2 and RanBP1 co-activator accelerate GTP hydrolysis, causing conformational opening that releases cargo and recycles receptor. Adapter proteins bridge RNAs and pre-ribosomal subunits to CRM1, including NMD3 for 60S subunit and PHAX for U snRNAs. Clathrin coats, dynein motors and SRP act in endocytosis, microtubule movement and ER targeting, not nuclear envelope crossing, underscoring specificity of leucine-rich NES-CRM1 system for maintaining compartmental proteome and preventing nuclear retention of signaling regulators.
Ref: Lodish et al., Molecular Cell Biology, 9th ed., Chapter 13: CRM1 Exportin Recognition of Leucine-Rich NES.