#GTPase

Cytoskeleton

Which GTPase is responsible for actin cytoskeleton rearrangements in HeLa cells?

Signal transduction from extracellular matrix and chemokines to actin cytoskeleton uses small GTPases of Rho subgroup cycling between GDP bound passive cytosolic state bound to GDI and GTP active membrane state driven by GEFs. In HeLa cervical carcinoma cells stimulated with lysophosphatidic acid or serum, RhoA GTP rapidly accumulates activating effectors ROCK1 2 that phosphorylate myosin light chain and LIMK restricting cofilin severing, and mDia1 formin nucleating unbranched filaments. Outcome is assembly of contractile stress fibers anchored at focal adhesions and enhanced cortical tension. Rac1 activation downstream of PI3K produces WAVE Arp2/3 dependent lamellipodia, Cdc42 activates N WASP Arp2/3 filopodia. Ran GTP gradient formed around chromosomes by RCC1 GEF controls spindle assembly and nuclear import export through importins, Rab GTPases mark endosomal compartments guiding vesicle trafficking via tethering complexes like HOPS CORVET. Experiments with C3 exoenzyme ADP rybosylating Rho abolish stress fibers, confirming Rho GTP drives actin rearrangements in HeLa and many non muscle cells responding to cues.

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 16: Rho GTPases and Actin Remodeling.

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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.

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Protein Sorting and Trafficking

Ran-GTP is primarily involved in:

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.

Ref: Gorlich & Kutay, Annu Rev Cell Dev Biol 1999, Ran Gradient. Alberts 7th ed., Chapter 12, Transport.

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A Cell Signaling

Overexpression of which GTPase in GTP-bound form modulates actin cytoskeleton?

Rho (GTP), is consistent with established principles of cell signaling, receptor pharmacology and cellular regulation. Experimental measurements of binding parameters, genetic loss-of-function studies and pharmacological interventions all converge on the same interpretation. Related options address neighboring concepts but do not satisfy the precise criterion stated in the question.

Ref: NCERT Biology Class 11–12 Alberts et al Molecular Biology of the Cell Lodish et al, Molecular Cell Biology Cooper & Hausman, The Cell Abbas et al., Cellular and Molecular Immunology (for immunology sections)

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