A selective filter for cytoplasmic transport at the axon initial segment.
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.
Song
Ai-Hong
AH
Institute of Neuroscience, State Key Laboratory of Neurobiology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Wang
Dong
D
Chen
Gang
G
Li
Yuju
Y
Luo
Jianhong
J
Duan
Shumin
S
Poo
Mu-Ming
MM
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
D000199:Actins; D017487:Ankyrins; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D014168:Transferrin; D050988:Vesicle-Associated Membrane Protein 2