Practice question
Question
Which GTPase is responsible for actin cytoskeleton rearrangements in HeLa cells?
Explanation
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.