On Aug. 18, Developmental Cell published online a paper entitled “Lgl1 Activation of Rab10 Promotes Axonal Membrane Trafficking Underlying Neuronal Polarization”. This work was mainly carried out by graduate students Tong Wang and Yang Liu, under the supervision of Dr. Zhen-Ge Luo.

Directed membrane trafficking is believed to be crucial for axon development during neuronal morphogenesis. However, the underlying mechanisms are poorly understood. In this work, the authors report a role of Lgl1, the mammalian homolog of Drosophila tumor suppressor Lethal giant larvae, in controlling membrane trafficking underlying axonal growth. They find that Lgl1 is associated with plasmalemmal precursor vesicles and enriched in developing axons. Lgl1 up-regulation promoted axonal growth, whereas down-regulation attenuated it as well as directional membrane insertion. Interestingly, Lgl1 interacted with and activated Rab10, a small GTPase which mediates membrane protein trafficking, by releasing GDP dissociation inhibitor (GDI) from Rab10. Furthermore, Rab10 lies downstream of Lgl1 in axon development and directional membrane insertion. Finally, both Lgl1 and Rab10 are required for neocortical neuronal polarization in vivo. Thus, the Lgl1 regulation of Rab10 stimulates the trafficking of membrane precursor vesicles, whose fusion with the plasmalemma is crucial for axonal growth.

Ongoing work of the group aims to determine the Rab10 effectors required for PPV formation, transportation, docking and fusion with the plasmalemma. These studies will provide further insights into mechanisms underlying directional membrane insertion during neuronal polarization and axon development.

Figure ： Lgl1 recruits Rab10 to PPV by releasing GDI. This regulation promotes directional membrane insertion and axon development.