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Fig. 10. Model for the regulation of endosome transport by RhoB-Dia1. (a) RhoB-GDP is internalised from the plasma membrane and activated on endosomes by an exchange factor, for example Vav2 (Gampel and Mellor, 2002). (b) RhoB-GTP recruits Dia1 and PRK1 (Mellor et al., 1998) to endosomes. RhoB activates Dia1 by relieving the autoinhibitory intramolecular interaction between the DAD domain and the Rho-binding domain (RBD). (c) Activated Dia1 interacts with unknown factors on endosomes and promotes actin assembly/elongation on endosomes through FH2-dependent actin nucleation and/or FH1-dependent recruitment of profilin-ATP-actin. Endosomal actin associates with actin fibres that run underneath the plasma membrane, by an as yet unknown mechanism, preventing the transfer of endosomes to microtubules and inhibiting further transport. (d) Finally, inactivation of RhoB prevents further actin polymerisation, the actin coat depolymerises and endosomes can then bind to microtubules via the minus-end directed motor dynein for transport toward the microtubule minus-end.





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