Kinesin light chain-independent function of the Kinesin heavy chain

In Drosophila, the asymmetries that specify the embryonic axes are established early during oogenesis in a process that requires the precise localisation of several transcripts (Riechmann and Ephrussi, 2001; van Eeden and St Johnston, 1999). The localisation of oskar mRNA to the posterior pole of the oocyte specifies where the pole plasm forms, and thus where the abdomen and the germ line will develop (Ephrussi and Lehmann, 1992; Kim-Ha et al., 1991). At early stage 9 of oogenesis, oskar mRNA starts accumulating in a crescent at the posterior pole of the oocyte, where it stays until the early stages of embryogenesis (Ephrussi et al., 1991; Kim-Ha et al., 1991). Treatments with microtubule-depolymerising drugs disrupt this posterior localisation, indicating that it requires an intact microtubule cytoskeleton (Clark et al., 1994). Furthermore, the localisation of oskar mRNA seems to correlate with the organisation of the microtubules in the oocyte. During stages 7-8, a signal from the posterior follicle cells induces reorganisation of the oocyte cytoskeleton, to form an anterior to posterior gradient of microtubules that persists until stage 10 (Lane and Kalderon, 1994; Ruohola et al., 1991; Theurkauf et al., 1992). A marker for the plus-ends of microtubules, the motor domain of Kinesin heavy chain fused to β-Galactosidase (Kin-βGal) localises to the posterior during these stages, whereas the putative minus-end marker, nod-βGal, and the MTOC component, Centrosomin, localise to the anterior (Clark et al., 1994; Clark et al., 1997; Brendza et al., 2000). In addition, the microtubules at the anterior of the oocyte are more resistant to short treatments with microtubule-depolymerising drugs, indicating that the more stable minus ends lie at this pole (Theurkauf et al., 1992). Thus, the microtubule cytoskeleton appears to be organised with the majority of the minus ends at the anterior, with the plus ends extending towards the posterior pole (Cha et al., 2001; Theurkauf et al., 1992). Mutants in the heavy chain of the plus end-directed microtubule motor protein, Kinesin I abolish the posterior localisation of oskar mRNA (Brendza et al., 2000). These results suggest that Kinesin I actively transports oskar mRNA along microtubules towards the plus ends at the posterior pole. However, Cha et al. have recently shown that microtubule minus ends are associated with most of the oocyte cortex (Cha et al., 2002). As they detect oskar mRNA around the entire cortex of Kinesin heavy chain (Khc) mutant germline clones, they propose that Kinesin transports the RNA away from all regions of the cortex except the posterior pole. According to this model, Kinesin functions to exclude oskar mRNA from the anterior and lateral cortex, and another mechanism must therefore somehow deliver it to the posterior pole. Conventional Kinesin, Kinesin I, was the first member of the Kinesin superfamily to be identified, and is responsible for the ATP-dependent transport of several distinct cargoes along microtubules, such as vesicles, membranous organelles and pigment granules (Brady, 1985; Goldstein and Yang, 2000; Vale et al., 1985; Yang et al., 1989). Kinesin I is composed of two Kinesin heavy chains (KHC) and two Kinesin light chains (KLC), each of which is encoded by several genes in vertebrates, but single-copy genes in Drosophila. The KHC has an N-terminal motor domain that contains both the microtubule and ATP binding sites, a central coiled-coil domain that 5473 Development 129, 5473-5485 © 2002 The Company of Biologists Ltd doi:10.1242/dev.00119