title: Lgl1 activation of rab10 promotes axonal membrane trafficking underlying neuronal polarization.
abstract: Directed membrane trafficking is believed to be crucial for axon development during neuronal morphogenesis. However, the underlying mechanisms are poorly understood. Here, we report a role of Lgl1, the mammalian homolog of Drosophila tumor suppressor Lethal giant larvae, in controlling membrane trafficking underlying axonal growth. We find that Lgl1 is associated with plasmalemmal precursor vesicles and enriched in developing axons. Lgl1 upregulation promoted axonal growth, whereas downregulation attenuated it as well as directional membrane insertion. Interestingly, Lgl1 interacted with and activated Rab10, a small GTPase that 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.
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Xu
authors.forename: Cai-Yun
authors.initials: CY
authors.lastname: Deng
authors.forename: Kong-Yan
authors.initials: KY
authors.lastname: Wu
authors.forename: Ji
authors.initials: J
authors.lastname: Zhu
authors.forename: Xiu-Qing
authors.initials: XQ
authors.lastname: Fu
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.forename: Zhen-Ge
authors.initials: ZG
authors.lastname: Luo
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D002478:Cells, Cultured; D015536:Down-Regulation; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D015854:Up-Regulation; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: C120070:CrispId2 protein, rat; D020730:Guanine Nucleotide Dissociation Inhibitors; D011506:Proteins; C082378:Rab10 protein, rat; D020691:rab GTP-Binding Proteins