Effectors of Rab GTPases: Rab Binding Specificity and Their Role in Coordination of Rab Function and Localization - Ras Superfamily Small G Proteins: Biology and Mechanisms 2 - page 57

Fig. 3.6 Schematic representation of Rab-GEF cascades. Active/GTP-bound Rab proteins are
shown in green , and inactive/GDP-bound Rab proteins are colored in red . The effector proteins/
complexes are depicted in blue (RBD) and gray (GEF domain)
EEA1, another Rab5 effector, which binds PI3P via its FYVE domain (Stenmark
et al. 1996 ). Rabenosyn-5 recruitment also requires this feedback via PI3P binding
(Nielsen et al. 2000 ).
The combination of feedback loops with cascades is very essential as certain
threshold concentrations of Rab proteins on the membrane will have to be reached
to achieve efficient effector recruitment. After the first recruitment of a Rab protein
to its target membrane feedback, loops (in combination with the already present
GEF protein) will ensure the accumulation of this Rab protein on the membrane
domain. Only after a certain threshold is reached, the effector protein of this Rab
protein will be recruited efficiently due to the relatively low affinity of the effector
proteins as discussed earlier. This effector protein will in turn recruit, via its GEF