The Role of Selective Transport in Neuronal Polarization Takashi Namba, 1,2 Shinichi Nakamuta, 1 Yasuhiro Funahashi, 1,2 Kozo Kaibuchi 1,2 1 Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, Showa, Nagoya 466-8550, Japan 2 CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan Received 27 September 2010; revised 4 January 2011; accepted 11 January 2011 ABSTRACT: Neurons are functionally and morpho- logically polarized and possess two distinct types of neu- rites: axons and dendrites. Key molecules for axon forma- tion are transported along microtubules and accumulated at the distal end of the nascent axons. In this review, we summarize recent advances in the understanding of the mechanisms involved in selective transport in neurons. In addition, we focus on motor proteins, cargo, cargo adap- tors, and the loading and unloading of cargo. ' 2011 Wiley Periodicals, Inc. Develop Neurobiol 71: 445–457, 2011 Keywords: kinesin; cargo adaptor; neuronal polarization; selective transport INTRODUCTION Neurons are highly polarized cells with two distinct types of neurites: axons and dendrites. Axons are typ- ically long and thin and contain synaptic vesicles from which they release chemical signals, called neu- rotransmitters, at axon terminals in response to elec- trical signals. In contrast, the dendrites are relatively short and thick. The dendrites contain neurotransmit- ter receptors and receive chemical signals from other neurons at the dendritic spines. Thus, neurons are polarized both morphologically and functionally. How neurons establish their polarity is one of the fun- damental issues in neuroscience. To study the polarization of neurons in vitro, Banker and colleagues developed a culture system of embryonic hippocampal neurons and observed the morphological changes that occur during polariza- tion (Dotti et al., 1988). Briefly, they showed that unpolarized neurons possess several immature neu- rites. Because these neurites are morphologically equivalent, the neurons are believed to remain in the unpolarized stage. Then, one of these immature neu- rites initiates a rapid elongation. This neurite becomes much longer than the other neurites and develops into a mature axon. The other remaining neurites remain relatively short during development and become dendrites. Therefore, the mature neurons possess an asymmetric morphology. Neurite exten- sion is driven by several different events as follows (Arimura and Kaibuchi, 2007; Witte and Bradke, 2008; Barnes and Polleux, 2009): an increase in cytoskeletal organization, such as actin disassembly and microtubule assembly; the local concentration and activation of signaling molecules, such as neuro- trophin Trk receptors and phosphoinositide 3-kinase (PI3K); and plasma membrane expansion that results Correspondence to: K. Kaibuchi (kaibuchi@med.nagoya-u.ac.jp). Contract grant sponsor: Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Agency (JST). Contract grant sponsor: Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT); contract grant number: (S) 20227006 (to K.K.). Contract grant sponsor: Japan Society for the Promotion of Sci- ence (JSPS); contract grant number: 15GS0319 (to K.K.). Contract grant sponsor: grants-in-aid for JSPS Fellows; contract grant number: 20-4053 (to S.N.). ' 2011 Wiley Periodicals, Inc. Published online 20 January 2011 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/dneu.20876 445