Halo: A Guiding Light for Transport

Abstract

Motor-powered transport along microtubule tracks plays a critical role in cell division and the generation of cell polarity [1]. It is now clear that individual cargoes, including kinetochores, melanosomes, neuronal vesicles and lipid droplets, associate with both plus enddirected and minus end-directed motor proteins and exhibit back and forth motion [1]. Poorly understood mechanisms ensure that only one type of motor is active at any given moment so as to prevent energyconsuming tugs-of-war (for example, see [2,3]). How are motors of one type turned off while motors of the opposing type are turned on? And how is this decision regulated such that long-range or net directional transport can occur? Answers to both of these questions might come from studies of Halo and a related family of proteins, the discovery of which was reported by Gross et al. [4] in a recent issue of Current Biology. The identification of Halo began with a screen of Drosophila deficiency (deletion) mutants for defects in lipid droplet transport [4]. Embryos deficient for any of several overlapping deficiencies exhibited defects in the net inward transport of lipid droplets. Subsequent rescue experiments with cloned DNAs showed that these defects are due to loss of halo gene activity. The observed transport defects are highly stage-specific, manifesting themselves only during an approximately 15 minute window just before cellularization of the syncytial embryo. In wild-type embryos, this stage is characterized by increased translucence (clearing) of the peripheral cytoplasm. In halo mutants the peripheral cytoplasm fails to clear, and instead a hazy brown ‘halo’ develops around the central yolk deposit. The clearing of lipid droplets from the peripheral cytoplasm requires net directional transport toward the plus ends of microtubules, which are organized around the center of the embryo. Such net transport can be seen at the level of individual lipid droplets by measuring run lengths — uninterrupted travel distances — in the minus and plus end directions [4,5]. In wild-type embryos, just before cellularization the mean runs in the plus end direction increase in length relative to mean runs in the minus end direction. In halo mutants, the opposite occurs: mean run lengths increase in the minus end direction and decrease in the plus end direction [4]. The differences in mean run lengths in wild-type embryos and halo mutants are not due to differences in the speed of transport, but rather to differences in the durations of the runs [4]. Specifically, Halo increases the duration of plus end runs and decreases the duration of minus end runs (Figure 1). Experiments with optical tweezers, used to measure the amount of force needed to stall lipid droplet transport, indicate that Halo strengthens the binding between plus end motors and microtubules and weakens the binding between minus end motors and microtubules [4]. These alterations in binding strength may affect run durations by changing the frequency with which motor proteins dissociate from microtubules. High observed variance in the stalling forces suggests that Halo may modulate binding strength by controlling the number of motors that bind microtubules, rather than the tenacity with which single motors bind [4–6]. How might Halo induce these changes in binding strength? One possibility is that Halo acts on a shared component of plus end and minus end motor complexes. For example, Halo might induce a conformational change in a shared factor which allosterically promotes strong binding of plus end motors to microtubules and thus runs of long duration. Reciprocally, the same conformational change might promote only weak binding of minus end motors to microtubules and thus runs of short duration. That opposite polarity motors share co-factors is suggested by studies in several systems which have shown that inhibition of either kinesin or dynein impairs transport in both directions [2,7–9]. Moreover, p150Glued has been shown to bind to dynein and kinesin in a competitive fashion and to be Dispatch Current Biology, Vol. 13, R869–R870, November 11, 2003, ©2003 Elsevier Science Ltd. All rights reserved. DOI 10.1016/j.cub.2003.10.046

DOI: 10.1016/j.cub.2003.10.046

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Cite this paper

@article{Cohen2003HaloAG, title={Halo: A Guiding Light for Transport}, author={Robert S . Cohen}, journal={Current Biology}, year={2003}, volume={13}, pages={R869-R870} }