Of Yeast, Mice, and Men

A typical eukaryotic cell contains many types of membrane organelles with characteristic distributions within the cyto-plasm. This distribution is facilitated in part by the organelle binding to a specific subset of motor proteins. Bound motors then transport the organelles to their proper destinations in the cell by moving them along microtubules or actin filaments. A key question of modern cell biology is how motor proteins recognize their target organelles. A number of recent articles address this question by showing that Rab proteins on the surface of organelles can function as a part of the recognition complex for motor proteins. Rab proteins form the largest branch of the Ras super-family of GTPases. They are found in organisms from yeast to human, and have been implicated in various functions within the cell including growth, protein trafficking, and the targeting and fusion of membrane bound or-in this issue, address the possibility that Rab proteins may also mediate motor/cargo interactions. They present compelling evidence to support this idea, while at the same time providing important information about some of the human disorders associated with organelle transport. The most comprehensive evidence for the involvement of Rab proteins in intracellular transport is provided by recent studies demonstrating interactions between Rab proteins and the organelle-transporting motors of the myosin-V class in several experimental systems (Pruyne et al., 1998; Schott et al., 1999). Class V myosins are processive plus-end directed motors that have been implicated in intracellular transport in all eukaryotes from yeast to humans. They consist of two identical heavy chains and twelve light chains. The heavy chains contain an NH 2-terminal motor domain, a neck region with binding sites for light chains, a coiled-coil stalk, and a COOH-terminal globular domain that is involved in cargo binding (Reck-Peterson et al., 2000). The first suggestion of a Rab/myosin-V interaction was provided by Pruyne et al. (1998) who showed that Myo2p, a yeast class V myosin, and Sec4p, a yeast Rab protein, colocalized to the growing bud in yeast cells (Pruyne et al., 1998). By using yeast with a conditional mutation in the MYO2 gene they were able to show that the localization of Sec4p was Myo2p dependent. Genetic evidence of an interaction between these two proteins in yeast was demonstrated by Schott et al. (1999) who showed that a mutation in MYO2 was synthetically lethal with a mutation in SEC4. A direct physical interaction between Rab proteins and …