Small GTPase Rab39A interacts with UACA and regulates the retinoic acid-induced neurite morphology of Neuro2A cells

• UACA functions as a specific GTP-Rab39A/B-binding protein.
• The Rab39A/B-binding site maps to the C-terminus of UACA.
• UACA colocalizes with Rab39A/B in cultured cells.
• Rab39A and UACA regulate neurite morphogenesis of differentiated Neuro2A cells.

We screened for a Rab39-specific effector by performing a yeast two-hybrid assay with GTP-locked Rab39A/B as the bait and identified UACA (uveal autoantigen with coiled-coil domains and ankyrin repeats) as a specific Rab39A/B-binding protein. Deletion analysis revealed that a C-terminal coiled-coil domain of UACA functions as a GTP-dependent Rab39-binding domain. shRNA-mediated knockdown of endogenous Rab39A or UACA in mouse neuroblastoma Neuro2A cells resulted in a change in retinoic acid-induced neurite morphology from a multipolar morphology to a bipolar morphology. Taken together, these findings indicate that UACA functions as a Rab39A effector in the retinoic acid-induced differentiation of Neuro2A cells.