Myosin Vb controls biogenesis of post-Golgi Rab10 carriers during axon development

Polarized membrane addition is crucial for axon development and elongation during neuronal morphogenesis. This process is believed to be regulated by directed membrane trafficking of Rab10-containing post-Golgi carriers. However, the mechanisms underlying the biogenesis of these carriers remain unclear. Here, we report that Rab10 interaction with myosin Vb (MYO5B) determines the formation of Rab10 carriers and is important for axon development. Rab10 interacts with the exon D-encoded domain of MYO5B. Downregulating the expression of MYO5B (+D) or blocking its interaction with Rab10 impairs the fission of Rab10 vesicles from trans-Golgi membranes, causes a decrease in the number of Rab10 transport carriers and inhibits axon development in cultured hippocampal neurons. Furthermore, the MYO5B–Rab10 system is required for axon development of vertebrate neocortical neurons or zebrafish retinal ganglion cells in vivo . Thus, specific interaction between Rab10 and MYO5B controls the formation of Rab10 vesicles, which is required for axon development. Polarized membrane addition during axon development requires post-Golgi Rab10 carriers, whose biogenesis mechanisms remain unknown. This work shows that specific interaction between Rab10 and MYO5B controls formation of the Rab10 carriers, and this process is essential for neuronal polarization.