Lipid droplets lead a Spartin existence

KRas takes a dif ferent route T he small GTPase KRas moves between different membranes within the cell by diffusion, but Lu et al. fi nd it can use an alternative mode of transport to travel to another destination. Ras proteins control many cellular functions including proliferation, differentiation, and apoptosis. Their location within the cell affects the downstream signals they send; KRas has been identifi ed at the plasma membrane and on intracellular membranes. Previous reports suggested that KRas associates with negatively charged membranes via its positively charged C-terminus and moves between compartments by diffusing through the cytosol along an electrostatic gradient. But when Lu et al. tracked GFP-labeled KRas, they discovered that the protein moves to early endosomes by internalizing from the plasma membrane in clathrin-coated vesicles. Unlike other Ras family members, KRas then gets sorted into late endosomes (LEs) before traveling to the lysosomes for degradation. Fluorescent probes revealed that KRas was active on LEs, where it colocalized with a scaffolding complex called p14-MP1 and initiated a MAP kinase signaling cascade. KRas' journey to the lysosomes is stimulated by EGF and its receptor, which share the ride all the way to the end, suggesting that lysosomal-degradation may be important for switching off the EGF/KRas signal. Indeed, when lysosomal degradation was blocked, the MAP kinase cascade remained active for longer on the LEs. The researchers now want to look at how LE KRas signaling is propagated and determine how it differs from KRas signaling at the plasma membrane. S partin, a protein linked to the neu-ronal disease Troyer syndrome, was thought to function in endocytosis. Here, Eastman et al. identify an unexpected role for Spartin in regulating the cell's lipid storage depots. Cells transport excess fats into lipid droplets (LDs), where they are kept until needed as sources of energy, but little is known about LD formation and regulation. Spartin hadn't been connected to LDs. But Eastman et al. found that Spartin localizes to LDs and binds to a known LD protein called TIP47. Spartin seems to regulate LD turnover: overexpressing or knocking down the protein caused an increase in both the organelle's size and number. In turn, Spartin is regulated by ubiquitination by the ubiquitin ligase WWP1. Overexpressed WWP1 removed Spartin from LDs and promoted its degradation. A truncated form of Spartin found in a rare neuronal disease called Troyer syndrome didn't localize to LDs or bind to …