title: A selective filter for cytoplasmic transport at the axon initial segment.
abstract: Distinct molecules are segregated into somatodendritic and axonal compartments of polarized neurons, but mechanisms underlying the development and maintenance of such segregation remain largely unclear. In cultured hippocampal neurons, we observed an ankyrin G- and F-actin-dependent structure that emerged in the cytoplasm of the axon initial segment (AIS) within 2 days after axon/dendrite differentiation, imposing a selective filter for diffusion of macromolecules and transport of vesicular carriers into the axon. Axonal entry was allowed for KIF5-driven carriers of synaptic vesicle protein VAMP2, but not for KIF17-driven carriers of dendrite-targeting NMDA receptor subunit NR2B. Comparisons of transport rates between chimeric forms of KIF17 and KIF5B, with the motor and cargo-binding domains switched, and between KIF5 loaded with VAMP2 versus GluR2 suggest that axonal entry of vesicular carriers depends on the transport efficacy of KIF-cargo complexes. This selective AIS filtering may contribute to preferential trafficking and segregation of cellular components in polarized neurons.
authors.affiliation: Institute of Neuroscience, State Key Laboratory of Neurobiology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Ai-Hong
authors.initials: AH
authors.lastname: Song
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Yuju
authors.initials: Y
authors.lastname: Li
authors.forename: Jianhong
authors.initials: J
authors.lastname: Luo
authors.forename: Shumin
authors.initials: S
authors.lastname: Duan
authors.forename: Mu-Ming
authors.initials: MM
authors.lastname: Poo
mesh_terms: D000199:Actins; D000818:Animals; D017487:Ankyrins / Q000378:metabolism; D001370:Axonal Transport; D001369:Axons / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism
chemical_list: D000199:Actins; D017487:Ankyrins; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D014168:Transferrin; D050988:Vesicle-Associated Membrane Protein 2