Cell, Vol. 112, 467–480, February 21, 2003, Copyright 2003 by Cell PressReviewThe Molecular Motor Toolboxfor Intracellular Transporttransport involves molecular motor proteins that carrycargo directionally along a cytoskeletal track (myosinsalong actin and kinesins and dyneins along microtu-Ronald D. Vale*Department of Cellular and MolecularPharmacologyHoward Hughes Medical Institute bules). Recent genomic sequencing projects have un-covered the complete inventories of molecular motorsUniversity of California, San Francisco513 Parnassus Avenue in several organisms. Such data, combined with infor-mation from functional studies, are providing clues onSan Francisco, California 94143the origins of the molecular motors and the intracellulartransport strategies employed by various organisms.While prokaryotes contain cytoskeletal filaments, theEukaryotic cells create internal order by using proteinmotors to transport molecules and organelles along cytoskeletal motors appear to be an early eukaryoticinvention. Several types of cargo-transporting molecularcytoskeletal tracks. Recent genomic and functionalstudies suggest that five cargo-carrying motors motors emerged in unicellular eukaryotes, and this sameancient “Toolbox” of motors expanded to meet the ma-emerged in primitive eukaryotes and have been widelyused throughout evolution. The complexity of these jority of transport needs of multicellular organisms.These cargo-transporting motors will be the focus of this“Toolbox” motors expanded in higher eukaryotesthrough gene duplication, alternative splicing, and the review. Molecular motors also are used for organizingcytoskeletal filaments (e.g., controlling their dynamics,addition of associated subunits, which enabled newcargoes to be transported. Remarkably, fungi, para- collecting them into bundles, and causing filament-fila-ment sliding). Intracellular transport also can be drivensites, plants, and animals have distinct subsets ofToolbox motors in their genomes, suggesting an by attaching cargo to the ends of polymerizing or depo-lymerizing microtubule or actin filaments. However,underlying diversity of strategies for intracellulartransport. these aspects of motor function and cytoskeletal dy-namics will not be discussed here.A cell, like a metropolitan city, must organize its bustlingcommunity of macromolecules. Setting meeting pointsProkaryotes Contain Cytoskeletal Filamentsand establishing the timing of transactions are of funda-Related to Actin and Tubulinmental importance for cell behavior. The high degree ofAlthough simpler in overall design than eukaryotes, pro-spatial/temporal organization of molecules and organ-karyotes also must physically separate replicated DNAelles within cells is made possible by protein machinesand establish a central division plane, and some bacteriathat transport components to various destinationshave well-defined asymmetric cell shapes. Recently,within the cytoplasm.several of the proteins involved in these processes wereLandmark discoveries of cytoplasmic transport havediscovered to be antecedents of eukaryotic actin andbeen, and continue to be, made through advances inmicrotubules (van den Ent et al., 2001a). FtsZ, whichmicroscopy. Intracellular motion was first observed informs filaments that encircle the middle of the bacteriumthe alga Chara by Bonaventura Corti in the late 18thduring septation, shows several striking similarities tocentury, and chromosome movements were docu-tubulin, including a superimposable three-dimensionalmented with remarkable accuracy by microscopists instructure, GTPase activity, and the ability to polymerizethe 19thcentury. The development of video-enhancedin vitro into microtubule-like polymers. FtsZ-like proteinscontrast microscopy in the early 1980s enabled the visu-also are found in chloroplasts where they participate inalization of small membranous organelles (Allen et al.,organelle replication. A second group of proteins (MreB,1982) and large protein complexes (Kozminski et al.,Mbl, and ParM) is related to actin. MreB has a similar1993). With this clearer view of the cell interior, the tre-three-dimensional structure to actin’s and polymerizesmendous amount of directed cytoplasmic motion be-in vitro into filaments that are similar but not identical tocame apparent. The use of the green fluorescent proteinactin filaments (van den Ent et al., 2001b). In B. subtilus,for tagging organelles, proteins, and RNA led to anotherMreB and Mbl form filamentous structures that respec-wave of discovery of intracellular movement. The list oftively encircle the middle and the longitudinal cell axestransported cargoes, which grows larger every year andjust beneath the membrane (Jones et al., 2001). Loss oftouches almost every aspect of cell and developmentaleither of these proteins (which are not found in sphericalbiology, now includes large membrane organelles (e.g.,bacteria) disrupts the rod-shaped morphology of B. sub-the Golgi and nucleus), smaller vesicular or tubular inter-tilis. ParM, on the other hand, serves a different functionmediates in the secretory and endocytic pathways, ain segregating replicated plasmids during cell divisionsubset of mRNAs, cytoskeletal filaments, proteins build-(Moller-Jensen et al., 2002).ing blocks for large macromolecular complexes such asWhile the existence of a bacterial cytoskeleton is nowcilia/flagella and centrosomes, and proteins involved inbeyond dispute, the manner in which these filamentssignaling and establishing cell polarity.perform their duties remains unclear. DepolymerizationThe most widely used mechanism for intracellularof FtsZ filaments might drive septation, and the polymer-ization of ParM has been proposed to drive the separa-tion of replicated plasmids (Moller-Jensen et al., 2002).*Correspondence: [email protected], bacterial filaments could undergo force- motors in the cargo-transporting Toolbox (Figure 1).Three of these are microtubule plus-end-directed kine-generating structural transitions (Erickson, 2001) orsins: conventional kinesin (also called kinesin I or KIF5),could serve as passive scaffolds for concentrating mole-kinesin II (also called heteromeric kinesin), and Unc104/cules (e.g., peptidoglycan synthetic or membrane fusionKIF1 (formerly called monomeric kinesin). Cytoplasmicmachineries in the case of FtsZ).dynein, which moves toward the microtubule minus end,Another possibility is that bacterial filaments serve asis another
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