Generation and Maintenance of Neuronal Polarity Mechanisms of Transport and Targeting

cell body and dendrites. Indeed, KIFC2, the only known minus end–directed kinesin-like protein, has been shown to localize almost exclusively to the somatodendritic portion of the neurons (Saito et al., 1997). While it remains unclear which organelles are transported by KIFC2, this motor is a good candidate for dendrite-spe-Stanford, California 94305 cific trafficking. However, the predominant localization of the plus end–directed motor protein (KIF21B) to the soma and dendrites appears inconsistent with this Neurons are highly polarized cells that provide a fasci-model, since such motors would be expected to eventu-nating example of how cellular morphology and accu-ally move into neuronal axons (Marszalek et al., 1999). rate protein distribution lay the basis for their function: Several mechanisms could account for the apparent the ability to receive, process, and transmit information. enrichment of KIF21B in neuronal dendrites. It is possi-Several cellular mechanisms contribute to the establish-ble that inactive KIF21B is transported into the dendrites ment and maintenance of neuronal polarity. As dis-by a minus end–directed motor, where it would remain sequestered until needed. Alternatively, the stability of cussed in the minireview by Winckler and Mellman (1999 KIF21B could be differentially regulated in axonal versus [this issue of Neuron]), protein sorting and targeting mo-dendritic processes. Indeed, differences in protein deg-tifs, the machinery that recognizes these motifs, as well radation rates between axons and dendrites have been as diffusion barriers are critical, particularly in the initial previously reported. Thus, KIF21B could enter both ax-phases of generating polarized cells. In this minireview, ons and dendrites while becoming stabilized only in we focus on the cytoskeleton and its associated ele-dendrites, perhaps by binding to its cargo organelles. ments, motors involved in protein kinesis, and proteins The identification of various molecular motors in-important for targeting to particular subcellular domains. volved in directional transport of specific organelles has Regulation of Polarized Vesicle Trafficking allowed us to begin to understand the initial transport Intracellular transport is essential for the generation and steps in the sequence of polarized trafficking in neurons. maintenance of neuronal polarization because it is the Nevertheless, many questions still remain unanswered. primary mechanism for the distribution of materials nec-For example, the mechanisms regulating the dissocia-essary for axonal and dendritic function. Many proteins tion of cargo organelles upon delivery to their destina-are actively transported along microtubules in association remain unclear. Furthermore, and perhaps most tion with the trafficking of various membranous organ-importantly, almost nothing is known about …