Kinesin Delivers

What is it about movement in cells that commands our atten-tion? What biologist has not enjoyed turning a microscope on a cell, almost any cell, really, and watching all the commo-tion? When vesicles, mitochondria, chloroplasts, nuclei, or chromosomes move, we are being treated to an elegant, easily observable manifestation of molecular events. Decades of effort to understand intracellular movement have given rise to two of the great thrusts of modern cell biology: the study of which things go where, usually referred to as intracellular trafficking; and the identification of the protein machines that generate movement, the molecular motors. But we have an incomplete picture of how the cell's array of motor proteins gives rise to the variety of journeys that their cargoes make. The kinesin motors that generate movement along microtubule tracks are a case in point (Vale and Fletterick, 1997). As with other motor proteins, the dyneins or myosins, the study of kinesin by the methods of molecular genetics has demonstrated that kinesins are a large family of related motor proteins present across all eukaryotic phyla, and numbering 30–40 members in humans and mice (Kim and Endow , 2000; http://www.blocks.fhcrc.org/~kinesin). Most analysis of this diversity thus far indicates that different kinesins serve to move different cargoes in the cell (Manning and Snyder, 2000). So, where does the trafficking information for the motor proteins reside? What is the cargo " receptor " for kinesin, and what specific protein–protein interactions govern this important matchmaking in the cell? Most work on this question has focused on the first kinesin family member to be discovered, so-called " conventional " kinesin, or kine-sin-I. In the case of kinesin-I, the ER membrane protein ki-nectin has been proposed to be a cargo receptor, but its restricted cellular and phylogenetic distributions (Toyoshima and Sheetz, 1996; Goldstein and Gunwardena, 2000) have prompted some investigators to look further. This search has recently borne fruit: two groups have reported that kinesin-I binds to cargoes via a set of proteins involved in intracellular signaling (Bowman et al., 2000; Verhey et al., 2001). The proteins, JIP-1, JIP-2, and JIP-3, are thought to serve as scaffolding proteins for the c-Jun NH 2-terminal kinase (JNK) 1 signaling pathway (Davis, 2000). The high affinity and specificity of kinesin binding to the JIP proteins indicates that the complex pairing of motors and cargoes will soon be on the same footing with other protein–protein interactions essential to …