Axonal transport versus dendritic transport - Wiley Online Library

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The major machines that convert chemical energy to physical force in cells ..... ecule PSD-95/discs large/zona occludens-1 proteins. J Neurosci 22:5253–5258.

Axonal Transport versus Dendritic Transport Mitsutoshi Setou, Takahiro Hayasaka, Ikuko Yao PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho Kawaguchi, Saitama, Japan

Received 2 April 2003; accepted 4 September 2003


Neurons have polarized processes for information output and input, axons, and dendrites. This polarized architecture is essential for the neuronal function. An increasing number of molecular components that mediate neuronal polarity establishment have been characterized over the past few years. The vast majority of these molecules include proteins that act in scaffolding protein complexes to sustain the polarized anchoring of molecules. In addition, more signaling and cytoskeleton-associated proteins have been proposed for establishment of polarity. It has become evident that dendritic and axonal transport of molecules depends on scaffolding/adaptor proteins that are recognized by mo-

INTRODUCTION An emerging paradigm of recent cell biology research is that the static cellular states are not sufficient for the deployment of complex patterns of cellular morphology. Instead, regulation of multiple factors mediate the establishment of transient molecular complexes that generate signal transmission in cells. This additional information is finally fixed as a morphological change of the cell, providing a key for differentiation. The transient molecular complexes responsible for these changes are themselves subject to change and require force to maintain their proper states. The major machines that convert chemical energy to physical force in cells are the motor proteins. The kinesin superfamily proteins (KIFs) of molecular moCorrespondence to: M. Setou ([email protected]). Contract grant sponsor: Time’s Arrow and Biosignaling, PRESTO, JST (M.S.). © 2003 Wiley Periodicals, Inc. DOI 10.1002/neu.10324

lecular motors. Current and future research in the neuronal cell polarity will be focused on how different cargo molecules transmit their signals to the cytoskeleton and change its dynamic properties to affect the rate and direction of vesicular movement. In this review, we discuss recent evidence that scaffolding proteins can regulate motor motility and guidance by a mechanism of substrate-cytoskeletal coupling and amino acid modifications during polarized transport. © 2003 Wiley Periodicals, Inc. J Neurobiol 58: 201–206, 2004

Keywords: axon; dendrite; transport; KIF; motor; scaffold

tors regulate organelle transport (Hirokawa et al., 1998). These proteins hydrolyze ATP to mediate transport on microtubules and are thought to play a major role in long distance organelle transport. In addition, increasing evidence suggests that long distance selective cargo transport is mediated via KIF protein complexes with adaptor/scaffolding molecules (Vale, 2003). Therefore, the regulation of molecular motors is central to the understanding of cell biology. In this study, we attempt to determine whether a cytoskeleton motor regulator exists, and if so how it regulates motor proteins. Molecular motors are largely classified as myosins, dyneins, and kinesins (Hirokawa, 1998; Vale, 2003). The kinesins play important roles particularly in neurons. Kinesins are coded by a large molecular gene family, the KIFs (Miki et al., 2001, 2003). In neurons, KIFs are the main long-distance transporters towards the periphery (Hirokawa, 1998). For example, KIF1 motors can transport synaptic vesicle precursors to axonal compartments (Okada et al., 1995; Zhao et al., 2001) and KIF17 motors transport neurotransmitter receptors to dendrites (Setou et al., 2000; Guillaud et 201


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al., 2003; Wong et al., 2002). Many investigators have begun to elucidate the life cycle of these molecular motors (Vale et al., 2003).

REGULATION OF MOTORS Little is known about transcriptional regulation of molecular motor genes. Production of KIF17, a brainspecific kinesin, is regulated by the CREB pathway under NMDA activation in vivo (Wong et al., 2002), and in culture (Guillaud et al., 2003). KIF17 is the only KIF examined so far that has a CREB transcription factor binding sequence in its promoter region (Wong et al., 2002). Other potential transcriptional regulatory sequences in KIF gene promoters, such as AP1 binding sites, have been reported (Wong et al., 2002). Thus, the KIFs are not uniformly synthesized; they appear to be differentially regulated. The time scale of transcriptional regulation is from hours to days, whereas cargo loading and unloading requires a time frame of seconds to minutes. Some of the KIFs have been found in the nucleus and can be transported to different intracellular locations (Sekine et al., 1994; Macho et al., 2002). A KIF17 isoform, KIF17b, has been shown to modulate transcription by direct interaction with a transcription coactivator (Macho et al., 2002). Interestingly, a PDZ protein, CASK, which is a component of the LinKIF17 complex, can act as a transcriptional coactivator in cells (Hsueh et al., 2000). Therefore, proteins associated with KIF17 may have other roles in transcriptional regulation.

CARGO BINDING MECHANISM BY MOLECULAR MOTORS After synthesis, KIFs need to find specific cargoes. Gene targeting and mutant analysis of motor proteins have suggested that KIFs display individual cargo specificity in vivo (Otsuka et al., 1991; Tabish et al., 1995; Tanaka et al., 1998; Yonekawa et al., 1998; Zhao et al., 2001). Specificity of cargo recognition by molecular motors must take into account the total number of motor species. There are 45 KIF gene loci, and more than 60 KIF transcripts, including splice variants, are elucidated to exist in mice and humans (Aizawa et al., 1992; Nakagawa et al., 1997; Miki et al., 2001, 2003; Okazaki et al., 2002). Moreover, at least 20 KIFs have motor activity in vitro and are expressed in the same CA1 hippocampal neurons (Miki et al., 2001). Thus, this provides one rationale

specificity and some general rules regarding cargo recognition by molecular motors. Recently, a variety of sorting proteins have been identified as scaffolds between cargoes and molecular motors (Nakagawa et al., 2000; Setou et al., 2000, 2002), which can mediate the spatial sorting of surface proteins. For example, Mint1 (mouse lin10 homologue), a component of the Lin complex with CASK and Velis, binds to KIF17. This complex is responsible for dendritic vesicular transport of NMDA receptors (Setou et al., 2000; Wong et al., 2002; Guillaud et al., 2003). A summary of proteins that conform to the ReceptorAdaptor-Motor (RAM) model can be found at the website 2002/setou.shl (Setou, 2002). The direct binding of kinesin to phosphatidic acid (PA) or phosphatidylinositol (4,5)- bisphosphate (PIP2) (Manifava et al., 2001; Klopfenstein et al., 2002) might be involved in the vesicular recruitment of these motors. There might be other regulatory mechanisms that allow the temporal and spatial selection of cargoes, as various adaptor proteins are reported to mediate motor protein cargo recognitions (Table 1). Differential interactions between molecular motors and sorting proteins provide possibilities for regulatory mechanisms to account for intracellular transport. From the data described in Table 1, receptor-adaptor-motor interactions represent a basic strategy for binding of cargo by molecular motors. We have noticed a surprising variety of dendritic transport mechanisms that depend on specific PDZ proteins. It is intriguing that direct binding has been proposed for NR2B subunit for NMDA receptors, not for the NR1 subunit, which is a key backbone of NMDA receptors (Setou et al., 2000; Mok et al., 2002). Similarly, GluR2, but not GluR1 subunit of AMPA receptors, directly interacts with the motor-adaptor complex (Setou et al., 2002; Shin, 2003). Subunit exchange of glutamate receptors has been suggested to underlie synaptic change (Shi et al., 2001; Wong, 2001). Enhanced performance in several learning tests of mice overexpressing KIF17 has been detected (Wong et al., 2002). This indicates that glutamate receptor trafficking by KIFs serves as an important regulatory mechanism that may underlie higher brain functions. Reduction of KIF17 protein levels results in a down-regulation of NR2B subunits, concomitant with an increase in NR2A without a change in NR1 subunits (Guillaud et al., 2003). Mint1 knockout mice do not affect total NMDA receptor levels (Ho et al., 2003) which suggests that Mint1/CASK/Velis function is not constitutively transporting NMDA receptors. Targeted mouse mutations in Velis (Misawa et al., 2001) or PSD95 (Migaud et al., 1998) are also

AT vs. DT Table 1


Interactions between Motors and Cargo

Motor Rabkinesin Kinesin Unc104



rab6 PA PIP2

Echard et al., 1998 Manifava et al., 2001 Klopfenstein et al., 2002


Adaptors (including light chain)



Kinesin KIF3A/B KIF17 KIF5 GAKIN KIF13A KIF5 KIF5 KIF1B␣ KIF3A/B KIF1A Myosin V myo4p Myosin Va Myo2p

Light chain kap3-fodrin Mint1/Cask/velis Light chain DLG AP1 Light chain-JIP GRIP PSD-95;SAP90;SAP97 KAP3-APC Lipin-alpha-GRIP Light chain-GKAP She3p/She2p Melanophilin vac17p

Kinectin ? NR2B APP ? MP6R APOER2 GluR2 ? ? AMPAR ? mRNA Rab27a vac8p

Toyoshima et al., 1992 Takeda et al., 2000 Setou et al., 2000 Kamal et al., 2000, 2001 Hanada et al., 2000 Nakagawa et al., 2000 Verhey et al., 2001 Setou et al., 2002 Mok et al., 2002 Jimbo et al., 2002 Shin et al., 2003 Naisbitt et al., 2000 Kruse et al., 2002 Wu et al., 2002 Tang et al., 2003

reported to have no obvious phenotype in NMDA receptor targeting. Redundancy is the usual excuse for an absence of phenotype; however, it is highly possible that they have defects in higher functions.

POLARITY OF MOLECULAR MOTORS IN AXONS AND DENDRITES Once they find their cargo, the next question is how molecular motors find their own direction toward axons or dendrites (Burack et al., 2000). In vivo, microtubule polarity in proximal dendrites is mixed, while microtubules in axons are oriented with plus ends toward the axon terminal. In the distal dendrites, plus ends are directed toward the tips (Baas et al., 1988). Thus, plus end motors are required for distal dendrites. In C. elegans, mutants in kinesin genes, such as unc104 and osm-3, have been discovered. These two genes encode N-terminal motor domain type plus-end directed kinesin proteins. The unc104 kinesin is required to establish the axonal synaptic vesicle targeting (Otsuka et al., 1991), whereas osm-3 kinesin is required to establish the correct function of dendritic cilium (Tabish et al., 1995). In these animals, dendritic cilium is at the tip of dendrites. The mammalian homologue of Unc104, KIF1A/ KIF1Bbeta, acts as an axonal transporter, and that of Osm-3, KIF17, acts as a dendritic transporter. These results indicate that each kinesin has a distinct polarity function in vivo, either towards a dendritic direction or

Figure 1 The schematic model of a neuron reflecting the ratio of real area and volume.


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an axonal direction. However, the motor domains share more than 90% similarity in sequence. While the motility assays of KIF family ATPases in vitro have been well documented, the mechanisms that ensure the directionality of microtubule tracks in the cell are still poorly understood. There can be at least two mechanisms for sorting, one is that axonal and dendritic preference is defined by specific axonal and dendritic motors. Polarized recognition stems from motor domains. The other mechanism that can be envisioned is specific degradation of the motor proteins in axon or dendritic localizations. We would like to point out these mechanisms are not mutually exclusive. It is important to evaluate the volume of neuronal compartments. Let us imagine a model of a human spinal cord motor neuron. Assume that this neuron has 10 dendrites with a diameter of 10 ␮m and a length of 1 mm, and the cell body spans 80 ␮m. We also assume that a myelinated axon of 1 m length possesses a diameter of 20 ␮m and a 5 ␮m diameter in the periphery. Based upon these assumptions, the relative ratio of volume of dendrite versus cell body versus axon is 5:1:2000 (0.2%;0.05%;99.7%) (Fig. 1). It is surprising how much the volume of the axon predominates over the other compartments. Thus, the axon reflects over 99% of a neuronal cell. If we assume the protein turnover to be equal everywhere in neurons, ignoring local synthesis and degradation, a large amount should be transported in axons. Based upon the calculations above, the difference between the size of dendrites versus axons is nearly 400-fold. In contrast, a rough calculation of the lateral area of the cell body that connects with the axon indicates it is 40-fold smaller than dendrites (Fig. 1). Assuming that a molecular motor starts a journey from the cell body towards the distal ends of the cell, the motors will more likely find the larger entrance to dendritic processes. This is based upon the relative ratio of lateral of the cell body to dendrites versus axons and the narrow space connecting the axon to the cell body. However, the majority of the cargo is predicted to go toward axons, because the axonal volume is much larger than that of dendrites. The smaller area that regulates entry into axons from the cell body must reflect regulatory mechanisms that guide proteins (Nakata et al., 2003).

POLARIZED RECOGNITION BY MOTOR DOMAINS The most noticeable difference between KIF1 and KIF17 motor domains is that KIF1 has extra lysine

residues (K) in loop 11 (K-loop) (Kikkawa et al., 2000, 2001; Okada and Hirokawa, 2000). KIF5 also possesses lysines in the neck region (Thorn et al., 2000). These lysine residues have been suggested as an additional microtubule binding domain that binds a tubulin C-terminal end named E-hook (Kikkawa et al., 2001). In fact, KIF5 is known to bind the suitable length polyglutamylated (on E-hook) tubulins in overlay (Larcher et al., 1996). The C-terminal domains of tubulins are exposed on the surface of microtubules, and it was already proposed that they are involved in microtubule assembly and polarity control in proceeding works (Gundersen et al., 1998). From the published data, we can expect that KIF17 has little microtubule preference, while KIF1 or KIF5 has more preference for microtubules. The K-loop or lysine residues in the neck domain may function as the receiver of the signal of tubulin C-terminal modifications. Crystallization and cryo-EM of the KIF17 motor domain will clarify these hypotheses in an atomic level resolution in the future.

INSTABILITY OF TRANSPORT MACHINERY One of the landmark observations of regulations of kinesins is that they accumulate in proximal, and not in distal, regions of ligated axons (Hirokawa et al., 1991). Moreover, GFP-KIF17 directly goes to dendrites and does not return; therefore, the “disposable motor” concept may also be true for dendrite motor proteins (Guillaud et al., 2003). At this moment, the degradation pathways for KIFs have not been defined. AMPA receptor interacting protein GRIP1 has been shown to bind KIF5 heavy chain and localize KIF5 to dendrites in neurons. The terminal effect of GRIP1 on kinesin (Setou et al., 2002) can be interpreted by several hypotheses. One simple interpretation is that the GRIP-kinesin complex is stable in dendrites, rather than in axons. Similar binding protein-dependent localization of motors has been reported in myosins (Kruse et al., 2002). Degradation of the myosin motor is regulated in yeast (Tang et al., 2003) and has been proposed for establishment of polarity. Protein degradation pathways, such as ubiquitination, are a potential mechanism to account for motor protein turnover. Phosphorylation of high molecular neurofilament proteins is another mechanism that can allow uncoupling of motor-cargo interactions.

AT vs. DT

FINAL PERSPECTIVES A variety of post-translational modifications on chromatin histone proteins have been shown to influence gene transcription and cellular differentiation memory. Likewise, modifications of tubulin can influence morphogenetic processes (Schreiber and Bernstein, 2002). Just as acetylation, phosphorylation, and methylation of the histone proteins can result in changes in transcription, similarly, modifications of the tails of tubulin proteins can dramatically change the binding of MAPs, including KIFs, to microtubules. Moreover, the sequences of KIF tails may also be the target of various post-translational modifications. For example, the sequence of the KIF17 C-terminal tail (KRKKSKNSFGGEPL) contains four lysine and two serines that potentially provide substrates for regulatory phosphorylation, ubiquitination, sumoylation, and acetylation events. Future characterization of the effects of these modification enzymes on tubulins, motors, and binding scaffolds will provide new insights for the establishment of polarity of the neuronal architecture. We thank Dr. Hirokawa for valuable discussions.

REFERENCES Aizawa H, Sekine Y, Takemura R, Zhang Z, Nangaku M, Hirokawa N. 1992. Kinesin family in murine central nervous system. J Cell Biol 119:1287–1296. Baas PW, Deitch JS, Black MM, Banker GA. 1988. Polarity orientation of microtubules in hippocampal neurons: uniformity in the axon and nonuniformity in the dendrite. Proc Natl Acad Sci USA 85:8335– 8339. Burack MA, Silverman MA, Banker G. 2000. The role of selective transport in neuronal protein sorting. Neuron 26:465– 472. Echard A, Jollivet F, Martinez O, Lacapere JJ, Rousselet A, Janoueix-Lerosey I, Goud B. 1998. Interaction of a Golgi-associated kinesin-like protein with Rab6. Science 279:580 –585. Guillaud L, Setou M, Hirokawa N. 2003. KIF17 dynamics and regulation of NR2B trafficking in hippocampal neurons. J Neurosci 23:131–140. Gundersen GG, Kreitzer G, Cook T, Liao G. 1998. Microtubules as determinants of cellular polarity. Biol Bull 194:358 –360. Hanada T, Lin L, Tibaldi EV, Reinherz EL, Chishti AH. 2000. GAKIN, a novel kinesin-like protein associates with the human homologue of the Drosophila discs large tumor suppressor in T lymphocytes. J Biol Chem 275:28774 –28784. Hirokawa N. 1998. Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science 279: 519 –526. Hirokawa N, Sato-Yoshitake R, Kobayashi N, Pfister KK, Bloom GS, Brady ST. 1991. Kinesin associates with


anterogradely transported membranous organelles in vivo. J Cell Biol 114:295–302. Ho A, Morishita W, Hammer RE, Malenka RC, Sudhof TC. 2003. A role for Mints in transmitter release: Mint 1 knockout mice exhibit impaired GABAergic synaptic transmission. Proc Natl Acad Sci USA 100:1409 –1414. Hsueh YP, Wang TF, Yang FC, Sheng M. 2000. Nuclear translocation and transcription regulation by the membrane-associated guanylate kinase CASK/LIN-2. Nature 404:298 –302. Jimbo T, Kawasaki Y, Koyama R, Sato R, Takada S, Haraguchi K, Akiyama T. 2002. Identification of a link between the tumour suppressor APC and the kinesin superfamily. Nat Cell Biol 4:323–327. Kamal A, Almenar-Queralt A, LeBlanc JF, Roberts EA, Goldstein LS. 2001. Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP. Nature 414:643– 648. Kamal A, Stokin GB, Yang Z, Xia CH, Goldstein LS. 2000. Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I. Neuron 28:449 – 459. Kikkawa M, Okada Y, Hirokawa N. 2000. 15 A resolution model of the monomeric kinesin motor, KIF1A. Cell 100:241–252. Kikkawa M, Sablin EP, Okada Y, Yajima H, Fletterick RJ, Hirokawa N. 2001. Switch-based mechanism of kinesin motors. Nature 411:439 – 445. Klopfenstein DR, Tomishige M, Stuurman N, Vale RD. 2002. Role of phosphatidylinositol(4,5)bisphosphate organization in membrane transport by the Unc104 kinesin motor. Cell 109:347–358. Kruse C, Jaedicke A, Beaudouin J, Bohl F, Ferring D, Guttler T, Ellenberg J, Jansen RP. 2002. Ribonucleoprotein-dependent localization of the yeast class V myosin Myo4p. J Cell Biol 159:971–982. Larcher JC, Boucher D, Lazereg S, Gros F, Denoulet P. 1996. Interaction of kinesin motor domains with alpha- and betatubulin subunits at a tau-independent binding site. Regulation by polyglutamylation. J Biol Chem 271:22117–22124. Macho B, Brancorsini S, Fimia GM, Setou M, Hirokawa N, Sassone-Corsi P. 2002. CREM-dependent transcription in male germ cells controlled by a kinesin. Science 298: 2388 –2390. Manifava M, Thuring JW, Lim ZY, Packman L, Holmes AB, Ktistakis NT. 2001. Differential binding of trafficrelated proteins to phosphatidic acid- or phosphatidylinositol (4,5)-bisphosphate-coupled affinity reagents. J Biol Chem 276:8987– 8994. Migaud M, Charlesworth P, Dempster M, Webster LC, Watabe AM, Makhinson M, He Y, Ramsay MF, Morris RG, Morrison JH, et al. 1998. Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein. Nature 396:433– 439. Miki H, Setou M, Hirokawa N. 2003. Kinesin superfamily proteins (KIFs) in the mouse transcriptome. Genome Res 13:1455–1465. Miki H, Setou M, Kaneshiro K, Hirokawa N. 2001. All


Setou et al.

kinesin superfamily protein, KIF, genes in mouse and human. Proc Natl Acad Sci USA 98:7004 –7011. Misawa H, Kawasaki Y, Mellor J, Sweeney N, Jo K, Nicoll RA, Bredt DS. 2001. Contrasting localizations of MALS/ LIN-7 PDZ proteins in brain and molecular compensation in knockout mice. J Biol Chem 276:9264 –9272. Mok H, Shin H, Kim S, Lee JR, Yoon J, Kim E. 2002. Association of the kinesin superfamily motor protein KIF1Balpha with postsynaptic density-95 (PSD-95), synapse-associated protein-97, and synaptic scaffolding molecule PSD-95/discs large/zona occludens-1 proteins. J Neurosci 22:5253–5258. Naisbitt S, Valtschanoff J, Allison DW, Sala C, Kim E, Craig AM, Weinberg RJ, Sheng M. 2000. Interaction of the postsynaptic density-95/guanylate kinase domain-associated protein complex with a light chain of myosin-V and dynein. J Neurosci 20:4524 – 4534. Nakagawa T, Setou M, Seog D, Ogasawara K, Dohmae N, Takio K, Hirokawa N. 2000. A novel motor, KIF13A, transports mannose-6-phosphate receptor to plasma membrane through direct interaction with AP-1 complex. Cell 103:569 –581. Nakagawa T, Tanaka Y, Matsuoka E, Kondo S, Okada Y, Noda Y, Kanai Y, Hirokawa N. 1997. Identification and classification of 16 new kinesin superfamily (KIF) proteins in mouse genome. Proc Natl Acad Sci USA 94:9654 –9659. Nakata T, Hirokawa N. 2003. Microtubules provide directional cues for polarized axonal transport through interaction with kinesin motor head. J Cell Biol 162:1045–1055. Okada Y, Hirokawa N. 2000. Mechanism of the singleheaded processivity: diffusional anchoring between the K-loop of kinesin and the C terminus of tubulin. Proc Natl Acad Sci USA 97:640 – 645. Okada Y, Yamazaki H, Sekine-Aizawa Y, Hirokawa N. 1995. The neuron-specific kinesin superfamily protein KIF1A is a unique monomeric motor for anterograde axonal transport of synaptic vesicle precursors. Cell 81:769 –780. Okazaki Y, Furuno M, Kasukawa T, Adachi J, Bono H, Kondo S, Nikaido I, Osato N, Saito R, Suzuki H, et al. 2002. Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature 420:563–573. Otsuka AJ, Jeyaprakash A, Garcia-Anoveros J, Tang LZ, Fisk G, Hartshorne T, Franco R, Born T. 1991. The C. elegans unc-104 gene encodes a putative kinesin heavy chain-like protein. Neuron 6:113–122. Schreiber SL, Bernstein BE. 2002. Signaling network model of chromatin. Cell 111:771–778. Sekine Y, Okada Y, Noda Y, Kondo S, Aizawa H, Takemura R, Hirokawa N. 1994. A novel microtubule-based motor protein (KIF4) for organelle transports, whose expression is regulated developmentally. J Cell Biol 127:187–201. Setou M, Nakagawa T, Seog DH, Hirokawa N. 2000. Kinesin superfamily motor protein KIF17 and mLin-10 in NMDA receptor-containing vesicle transport. Science 288:1796 –1802. Setou M. 2002. Cargo recognition mechanisms of molecular motors. Science 298:1568.

Setou M, Seog DH, Tanaka Y, Kanai Y, Takei Y, Kawagishi M, Hirokawa N. 2002. Glutamate-receptorinteracting protein GRIP1 directly steers kinesin to dendrites. Nature 417:83– 87. Shi S, Hayashi Y, Esteban JA, Malinow R. 2001. Subunitspecific rules governing AMPA receptor trafficking to synapses in hippocampal pyramidal neurons. Cell 105: 331–343. Shin H, Wyszynski M, Huh KH, Valtschanoff JG, Lee JR, Ko J, Streuli M, Weinberg RJ, Sheng M, Kim E. 2003. Association of the Kinesin Motor KIF1A with the Multimodular Protein Liprin-alpha. J Biol Chem 278:11393–11401. Tabish M, Siddiqui ZK, Nishikawa K, Siddiqui SS. 1995. Exclusive expression of C. elegans osm-3 kinesin gene in chemosensory neurons open to the external environment. J Mol Biol 247:377–389. Takeda S, Yamazaki H, Seog DH, Kanai Y, Terada S, Hirokawa N. 2000. Kinesin superfamily protein 3 (KIF3) motor transports fodrin-associating vesicles important for neurite building. J Cell Biol 148:1255–1265. Tanaka Y, Kanai Y, Okada Y, Nonaka S, Takeda S, Harada A, Hirokawa N. 1998. Targeted disruption of mouse conventional kinesin heavy chain, kif5B, results in abnormal perinuclear clustering of mitochondria. Cell 93:1147–1158. Tang F, Kauffman EJ, Novak JL, Nau JJ, Catlett NL, Weisman LS. 2003. Regulated degradation of a class V myosin receptor directs movement of the yeast vacuole. Nature 422:87–92. Thorn KS, Ubersax JA, Vale RD. 2000. Engineering the processive run length of the kinesin motor. J Cell Biol 151:1093–1100. Toyoshima I, Yu H, Steuer ER, Sheetz MP. 1992. Kinectin, a major kinesin-binding protein on ER. J Cell Biol 118: 1121–1131. Vale RD. 2003. The molecular motor toolbox for intracellular transport. Cell 112:467– 480. Verhey KJ, Meyer D, Deehan R, Blenis J, Schnapp BJ, Rapoport TA, Margolis B. 2001. Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules. J Cell Biol 152:959 –970. Wong RW, Setou M, Teng J, Takei Y, Hirokawa N. 2002. Overexpression of motor protein KIF17 enhances spatial and working memory in transgenic mice. Proc Natl Acad Sci USA 99:14500 –14505. Wu XS, Rao K, Zhang H, Wang F, Sellers JR, Matesic LE, Copeland NG, Jenkins NA, Hammer JA, 3rd. 2002. Identification of an organelle receptor for myosin-Va. Nat Cell Biol 4:271–278. Yonekawa Y, Harada A, Okada Y, Funakoshi T, Kanai Y, Takei Y, Terada S, Noda T, Hirokawa N. 1998. Defect in synaptic vesicle precursor transport and neuronal cell death in KIF1A motor protein-deficient mice. J Cell Biol 141:431– 441. Zhao C, Takita J, Tanaka Y, Setou M, Nakagawa T, Takeda S, Yang HW, Terada S, Nakata T, Takei Y, et al. 2001. Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta. Cell 105:587–597.

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