Temporal regulation of lipid-droplet motion
Left: The global distribution of lipid droplets in embryos changes stereotypically over the first few hours of embryogenesis. These changes are largely driven by regulated production and destruction of Halo.
Right: Halo ultimately causes changes in the length of travel in the plus-end direction and thus somehow modulates properties of kinesin-1. Halo likely acts in part through the droplet protein LSD-2 since Halo affects the phosphorylation state of LSD-2 and lack of LSD-2 disrupts proper temporal regulation of transport.
Lipid droplets are motile in many cells (Welte, 2009). Droplet motion is particularly vigorous in early Drosophila embryos (see movie); more detail on the movie page). These droplets move bidirectionally along microtubules, powered by the motors kinesin-1 and cytoplasmic dynein (Shubeita et al., 2008, Gross et al., 2000. Because many other intracellular cargoes move bidirectionally employing these same two motors, lipid droplets are a great model for uncovering general transport mechanisms.
The timing of droplet transport is highly regulated and occurs in stereotypic phases. Initially, the lipid droplets are found throughout the embryo periphery, then they pull away from the surface and accumulate around the central yolk, and finally they spread out into the periphery again (see cartoon and confocal movie; more detail on the movie page). These changes in lipid-droplet distribution come about by changes in the travel distances for kinesin-1 and dynein–based motion (Welte et al., 1998).
The key event for net inward transport is expression of the novel protein Halo (Gross et al., 2003. Halo determines overall directionality of transport, and its expression determines the timing of transport. The molecular mechanism of Halo-based regulation remains to be elucidated, but we do know that Halo modulates the phosphorylation state of the droplet protein LSD-2 (Welte et al., 2005 and ultimately controls the properties of kinesin-1 (Shubeita et al., 2008).
To fully understand temporal regulation of lipid-droplet motion, we are now
- Performing a structure-function analysis for Halo
- Searching for Halo’s molecular targets
- Investigating how Halo protein levels are temporally regulated
For other projects in the laboratory, please check out the links below: