A sorting protein uses the coincidence of a lipid signal and membrane curving to direct its tubulation activity to the correct compartment, as shown by Jez Carlton, Peter Cullen (University of Bristol, UK), and colleagues. Relatives of this sorting nexin, SNX1, may control trafficking to and from a number of intracellular compartments.
SNX1 chooses its home via two membrane-binding domains. One targeting domain is the PX domain, which is known to bind to the endosomal phosphoinositide, PI3P. The second is a BAR domain, which was shown to target a fly protein to highly curved membranes and tubulate them.
Cullen's group shows that these domains combine to put mammalian SNX1 on the tubular portion of early endosomes (which also have less curved vesicular domains). This placement was needed to recycle a mannose-6-phosphate receptor from endosomes to the TGN. The cargo is probably selected by the retromer complex, which associates with SNX1.
The pinching off of endosomal tubules may be SNX1-driven, but Cullen is not yet convinced, as he needed a lot of SNX1 to get tubulation in vitro. Nine SNX1 relatives have both BAR-like and PX domains. As mammalian PX domains have different PIP binding partners, the nine might direct various trafficking pathways.