Functional crosstalk between ARF and Rab small GTPases

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Small GTPases of the ARF family, except for ARF6, mainly localize to the Golgi apparatus, where they trigger formation of coated carrier vesicles. I found that the simultaneous depletion of ARF1/ARF3 or ARF1/ARF4 induced extensive tabulation of Rab4- and Rab11-positive recycling endosomes. Moreover, ARF1/ARF3 are redundantly required for recycling pathway from the recycling endosomes to the plasma membrane. On the other hand, ARF1/ARF4 are redundantly required for the retrograde transport of TGN38 and mannose-6-phosphate receptor from recycling endosomes to the the trans-Golgi network (TGN), but was not required for the recycling pathway. It remains important to determine how distinct combinations of ARFs sort cargos targeted to distinct organelles and regulate separate transport processes on the same compartments. ARFs may act within distinct membrane microdomains along with distinct effector proteins.