Kinesin transport

Another form of dynein, called cytoplasmic dynein, is a molecular motor that transports materials from the plus end of the microtubule toward the minus end. The protein kinesin transports them in the opposite direction. 

MTs extend from the centrosome throughout the cytoplasm to the plasma membrane, where they are stabilized by caps. Sliding along the MTs, kinesin and dynein motors transport their cargoes between the center and the periphery of the cell. MTs present in the axons of neur ons are extended not only by addition of heterodimers to the plus ends but also by use of short MTs that initiate in the centrosome. Their axonal transport is mediated by dynein motors that are passively moved along actin filaments. Once formed in the axon, MTs serve as tracks for the fast axonal transport, i.e. the movement of membranous organelles and membrane proteins to the nerve ending. 

The membrane tubules and lamellae of the endoplasmic reticulum (ER) are extended in the cell with the use of MTs and actin filaments. Kinesin motors are required for stretching out the ER, whereas depolymerization of microtubules causes the retraction of the ER to the cell centre in an actin-dependent manner. Newly synthesized proteins in the ER are moved by dynein motors along MTs to the Golgi complex (GC), where they are modified and packaged. The resulting vesicles move along the MTs to the cell periphery transported by kinesin motors. MTs determine the shape and the position also of the GC. Their depolymerization causes the fragmentation and dispersal of the GC. Dynein motors are required to rebuild the GC. 

Even though dynein, kinesin, and myosin serve similar ATPase-dependent chemomechanical functions and have structural similarities, they do not appear to be related to each other in molecular terms. Their similarity lies in the overall shape of the molecule, which is composed of a pair of globular heads that bind microtubules and a fan-shaped tail piece (not present in myosin) that is suspected to carry the attachment site for membranous vesicles and other cytoplasmic components transported by MT. The cytoplasmic and axonemal dyneins are similar in structure (Hirokawa et al., 1989 Holzbaur and Vallee, 1994). Current studies on mutant phenotypes are likely to lead to a better understanding of the cellular roles of molecular motor proteins and their mechanisms of action (Endow and Titus, 1992). 

Figure 6. Transport of material along the nerve axon. Materials such as neurotransmitter peptides are synthesized in the cell body and sequestered in vesicles at the Golgi. Vesicles are then transported down the axon towards the synapse by kinesin motors. Other materials are transported from the synapse to the cell body by dynein motors.

Kinesins Motor proteins for microtubule-based synaptic vesicle transport. In Caenorhabditis elegans, akinesin encoded by unc-104 is essential for transport of synaptic vesicles to nerve terminals. 

Kinesins mediate anterograde transport in a variety of organisms and tissues 495... 

Kinesins mediate anterograde transport in a variety of organisms and tissues. Since its discovery, much has been learned about the biochemical, pharmacological and molecular properties of kinesin [44, 45], Kinesin is the most abundant member of the kinesin family in vertebrates and is widely distributed in neuronal and nonneuronal cells. The holoenzyme is a heterotetramer comprising two heavy chains (115-130 kDa) and two light... 

In neurons and non-neuronal cells, kinesin is associated with a variety of MBOs, ranging from synaptic vesicles to mitochondria to lysosomes. In addition to its role in fast axonal transport and related phenomena in non-neuronal cells, kinesin appears to be involved in constitutive cycling of membranes between the Golgi and endoplasmic reticulum. However, kinesin is not associated with all cellular membranes. For example, the nucleus, membranes of the Golgi complex and the plasma membrane all appear to lack kinesin. Kinesin interactions with membranes are thought to involve the light chains and carboxyl termini of heavy chains. However, neither this selectivity nor the molecular basis for binding of kinesin and other motors to membranes is well understood. 

Systematic cloning strategies based on the conserved motor domain sequences have identified a remarkable number of KRPs expressed in brain. Members of several KRP families expressed in brain have been implicated in forms of MBO transport. Kinesin-2 family members have been implicated in assembly and maintenance of cilia and... 

Curiously, functions proposed for some brain KRPs [55] are very different from functions proposed for similar or identical KRPs in no-neuronal cells. For example, members of the kinesin-13 family have been implicated in both mitotic spindle function and in axonal membrane transport. Similarly, a mouse kinesin-4 was reported to associate with unidentified MBOs in neurites, but its chicken homolog bound to chromosomal DNA and mediates chromosome movements in the mitotic spindle. Finally, a kinesin-6 was originally found to have a role in mitotic spindle function, but members of the kinesin-6 family were also implicated in the transport of MTs into dendrites [56]. 

Cytoplasmic dyneins may have multiple roles in the neuron. The identification of kinesin as a plus-end directed microtubule motor suggested that it is involved in anterograde transport but left the identity of the retrograde motor an open question. Since flagellar dynein was known to be a minus-end-directed motor, interest in cytoplasmic dyneins was renewed. Identification of the cytoplasmic form of dynein in nervous tissue came as an indirect result of the discovery of kinesin. 

Hirokawa, N. Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science 279 519-526, 1998. 

Elluru, R., Bloom, G. S. and Brady, S. T. Fast axonal transport of kinesin in the rat visual system functionality of the kinesin heavy chain isoforms. Mol. Biol. Cell 6 21-40,1995. 

Goldstein, L. S. B. and Yang, Z. Microtubule-based transport systems in neurons the roles of kinesins and dyneins. Annu. Rev. Neurosci. 23 39-71, 2000. 

The axonal transport of APP in neurons is mediated by the direct binding of APP to the kinesin light chain subunit of kinesin I. An axonal membrane compartment contains APP, P-secretase, and PSl, and the fast anterograde axonal transport of this compartment is mediated by APP and kinesin I. APP proteolysis in this... 

Kamal, A., Almenar-Queralt, A., LeBlanc, J.F., Roberts, E.A., Goldstein, L.S.B. (2001) Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP. Nature, 414, 643-648. 

---