Molecular motors and mechanisms of directional transport in neurons

In neurons, most proteins that are needed in the axon are synthesized in the cell body and selectively transported to the axon. Most dendritic proteins are also selectively transported from the cell body, but several specific mRNAs are transported into dendrites to support local protein synthesis.For transport of membranous organelles, macromolecular complexes and mRNAs in the axons and dendrites, microtubules serve as rails and kinesin superfamily proteins (KIFs) function as anterograde motors. Microtubules have polarity, with a plus end and a minus end.Forty-five KIF genes have been identified in mice and humans. All kinesins have a motor domain that shows high degrees of homology. However, regions outside the motor domains are unique, and these regions allow various cargoes to be recognized and differentially transported.Recently, unified family names for classification of kinesins in all phylogenies (Kinesin 1 to Kinesin 14) have been defined, but individual motor names will remain the same. The KIF5 family corresponds to conventional kinesin.Most kinesins move towards the plus end of microtubules, which takes them from the cell body towards the nerve terminal. The KIF2 family is unique in having both plus-end-directed motor activity and microtubule-depolymerizing activity, which is used to control axon collateral extension at the growth cone.Adaptor/scaffolding proteins tend to be used for the binding of kinesins to cargoes. Examples are the use of the adaptor protein 1 (AP1) adaptor complex, scaffolding proteins, including proteins of the JNK signalling pathway called JIPs and glutamate receptor-interacting protein 1 (GRIP1), and a tripartite scaffolding protein complex containing LIN10, LIN2 and LIN7 for transporting selective membrane cargoes. The molecular interactions of kinesins, adaptor/scaffolding proteins and cargoes have been elucidated in detail in these examples.KIF5 transports various cargoes to both axons and dendrites. Both the carboxy-terminal tail of KIF5 and the associated light chain can serve as binding sites for cargoes, and they might be differentially used for selective transport. Cargoes bound to kinesin light chain tend to be transported to axons, whereas those bound to the KIF5 tail are transported to dendrites.mRNAs are transported in dendrites as a large multisubunit complex of 42 proteins that binds to the tail of KIF5.The microtubule bundle at the initial segment, which shows characteristically strong binding to EB1 (a microtubule-associated protein), serves as a cue for KIF5 to enter axons.Many mechanisms might be used to achieve selective transport of various cargoes. However, a basic understanding of the transport process from the viewpoint of motors and their association with cargoes will clarify the common principles of selective transport.