Endosomal Localization of Fip3/Arfophilin-1 and Its Involvement in Dendritic Formation of Mouse Hippocampal Neurons

Endosomal trafficking mediated by Rab11 and Arf6 small GTPases is essential for various neuronal functions. Family of Rab11-interacting protein 3 (FIP3)/Arfophilin-1, also termed Eferin, is a dual effector for Rab11 and Arf6 and implicated in endosomal trafficking during cytokinesis. To understand the neuronal functions of FIP3, we first showed the widespread neuronal expression of FIP3 mRNA in adult mouse brain by in situ hybridization. Immunohistochemical analysis showed the association of FIP3 with a subpopulation of endosomes labeled with EEA1 and syntaxin 12 in hippocampal neurons. Immunoblot analysis showed the progressive increase of FIP3 with a peak around postnatal day 15 during hippocampal development. Furthermore, knockdown of endogenous FIP3 decreased the total dendritic length of cultured hippocampal neurons with a concomitant increase in the number of short (<40μm) primary dendrites. Together, FIP3 is suggested to regulate dendritic formation possibly through Rab11- and Arf6-mediated endosomal trafficking.