The Nedd4-binding protein 3 (N4BP3) is crucial for axonal and dendritic branching in developing neurons

Background: Circuit formation in the nervous system essentially relies on the proper development of neurons and their processes. In this context, the ubiquitin ligase Nedd4 is a crucial modulator of axonal and dendritic branching.Results: Herein we characterize the Nedd4-binding protein 3 (N4BP3), a Fezzin family member, during nerve cell development. In developing rat primary hippocampal neurons, endogenous N4BP3 localizes to neuronal processes, including axons and dendrites. Transient in vitro knockdown of N4BP3 in hippocampal cultures during neuritogenesis results in impaired branching of axons and dendrites. In line with these findings, in vivo knockdown of n4bp3 in Xenopus laevis embryos results in severe alteration of cranial nerve branching.Conclusions: We introduce N4BP3 as a novel molecular element for the correct branching of neurites in developing neurons and propose a central role for an N4BP3-Nedd4 complex in neurite branching and circuit formation.