A major function of cytoskeletal motors in interphase cells is the transport and positioning of membrane-enclosed organelles (Movie 16.10). Kinesin was originally identified as the protein responsible for fast anterograde axonal transport, the rapid movement of mitochondria, secretory vesicle precursors, and various synapse components down the microtubule highways of the axon to the distant nerve terminals. Cytoplasmic dynein was identified as the motor responsible for transport in the opposite direction, retrograde axonal transport. Although organelles in most cells need not cover such long distances, their polarized transport is equally necessary. A typical microtubule array in an interphase cell is oriented with the minus ends near the center of the cell at the centrosome and the plus ends extending to the cell periphery. Thus, centripetal movements of organelles or vesicles toward the cell center require the action of minus-end directed cytoplasmic dynein motors, whereas centrifugal movements toward the periphery require plus-end directed kinesin motors. Interestingly, in animal cells, nearly all minus-end directed transport is driven by the single cytoplasmic dynein 1 motor, whereas 15 different kinesins are used for plus-end directed transport.
Figure 16–59 The power stroke of dynein. (A) The organization of the domains in each dynein heavy chain. This is a huge polypeptide, containing nearly 4000 amino acids. The number of heavy chains in a dynein is equal to its number of motor heads. (B) Illustration of dynein c, a monomeric axonemal dynein found in the unicellular green alga Chlamydomonas reinhardtii. The large dynein motor head is a planar ring containing a C-terminal domain (gray) and six AAA domains, four of which retain ATP-binding sequences, but only one of which (dark red) has the major ATPase activity. Extending from the head are a long, coiled-coil stalk with the microtubule-binding site at the tip, and a tail that attaches to an adjacent microtubule in the axoneme. In the ATP-bound state, the stalk is detached from the microtubule, but ATP hydrolysis causes stalk–microtubule attachment (left). Subsequent release of ADP and phosphate (Pi) then leads to a large conformational “power stroke” involving rotation of the head and stalk relative to the tail (right). Each cycle generates a step of about 8 nm, thereby contributing to flagellar beating (see Figure 16–65). In the case of cytoplasmic dynein, the tail is attached to a cargo such as a vesicle, and a single power stroke transports the cargo about 8-nm along the microtubule toward its minus end (see Figure 16–60). (C) Electron micrographs of purified monomeric dyneins in two different conformations representing different steps in the mechanochemical cycle. (C, from
S.A. Burgess et al., Nature 421:715–718, 2003. With permission from Macmillan Publishers Ltd.)