The family of small RhoGTPases plays a crucial role in the spatial and temporal coordination cell migration. GEFs, GAPs and GDIs are the enzymes that regulate their activity, although the mechanism is poorly understood. Regulation models proposed to date have focused on GEFs as the main modulators of RhoGTPase activity, leaving a passive role to GAPs and GDIs. In this work we show that this assumption leads to models with properties that may be inconsistent with observations, more precisely, appearance of Turing instabilities and reduced sensitivity to secondary stimuli. The mathematical basis of this behavior is established, and a general class of interaction schemes that bypass it by including GAP and GDI regulation, which is supported by experimental evidence, is proposed.

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