Neurons are polarized cells consisting of somatodendritic and axonal compartments that serve their input and output functions, respectively. Distinct molecules are segregated into somatodendritic and axonal compartments, but mechanisms underlying the development and maintenance of such segregation remain largely unknown.

Jointly supervised by Dr. Mu-ming Poo and Dr. Shu-min Duan, Ai-hong Song and others found that an ankyrin G- and F-actin-dependent structure emerges in the cytoplasm of the axon initial segment (AIS) within 2 days of axonal/dendritic differentiation, imposing a selective filter for diffusion of macromolecules and for transport of vesicular carriers into the axon. Axonal entry was accessible 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. The work was published online in Cell on March 5, 2009.