Skip to content
Login Register

#exportin

3 public questions tagged with this topic.

Protein Sorting and Trafficking

Which of the following processes is not directly dependent on Ran-GTP?

Most nuclear import of NLS proteins using importin-alpha-beta heterodimer and export of NES proteins via CRM1 strictly consume Ran-GTP cycles, with RCC1 generating Ran-GTP inside nucleus and RanGAP1 hydrolyzing outside. Each cycle consumes one GTP and relies on NTF2 recycling of Ran-GDP. Messenger RNA departure follows divergent energetic logic. Bulk poly(A) mRNA transcribed, spliced and polyadenylated recruits TREX complex and adaptor Aly/REF that loads heterodimer NXF1-NXT1 which binds FG repeats directly without Ran. At cytoplasmic filaments of pore, DEAD-box helicase Dbp5/DDX19 activated by Gle1 and IP6 hydrolyzes ATP to displace NXF1 and associated factors, remodeling particle and preventing back-diffusion, thus providing directionality. Because Ran not involved, dominant-negative Ran mutants or RCC1 inhibition arrest protein transport but leave mRNA export largely intact. Golgi transport uses Rab and Arf GTPases instead of Ran. Hence among nuclear processes listed, mRNA export represents classic Ran-independent pathway illustrating ATP-driven remodeling can substitute for GTP gradient to achieve vectorial movement across envelope while supporting continuous gene expression even during mitotic remodeling of envelope.

Ref: Stewart M, Nature Rev Mol Cell Biol 8: 2007, Ran-Dependent Protein Transport versus Ran-Independent mRNA Export.

View Details
Protein Sorting and Trafficking

Which GTPase is specifically involved in nuclear transport?

Ran is small 25 kilodalton Ras-family GTPase that specializes in marking nuclear versus cytoplasmic compartments, unlike Rab, Rho and Ras which control vesicle docking, actin remodeling and MAP kinase signaling elsewhere. Its nucleotide state differs across envelope because regulators are spatially segregated: RCC1 guanine nucleotide exchange factor bound to histones H2A-H2B inside nucleus generates high Ran-GTP, while RanGAP1 SUMOylated and anchored to RanBP2/Nup358 at cytoplasmic filaments together with RanBP1 accelerate GTP hydrolysis outside producing Ran-GDP. This partitioning creates steep gradient, nuclear Ran-GTP almost hundred-fold higher than cytoplasmic, providing chemical potential for transport. During import, importin heterodimer binds cargo where Ran-GTP low, traverses pore and meets Ran-GTP that dissociates complex. During export, high nuclear Ran-GTP promotes NES cargo association with exportins. Beyond transport, Ran-GTP gradient directs mitotic spindle assembly around chromosomes and nuclear envelope reformation after mitosis. Mutations locking Ran in GDP or GTP state inhibit both import and export and disrupt cell division, demonstrating dedicated role in compartment identity and cell cycle control beyond generic GTPase signaling.

Ref: Alberts et al., Molecular Biology of the Cell, 6th ed., Chapter 12: Ran GTPase Gradient, RCC1 and RanGAP.

View Details
Protein Sorting and Trafficking

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.

View Details