Sorting nexins (SNXs) are a family of proteins that involved in diverse intracellular endosomal trafficking pathways. They all contain a PX (phox-homology) domain. The PX domain, via binding to certain phosphoinositide lipids, is responsible for membrane attachment to organelles of the endosomal system. The PX domain mostly binds to PtdIns3P, although other specificities have been reported for a few SNXs.
It was previously reported that over expression of SNX10 could induce the formation of giant vacuoles in mammalian cells. Furthermore, an SNX10/V-ATPase regulated vesicular trafficking pathway was identified to be crucial during early embryonic development. More recently, several mutations in SNX10 have been linked to osteopetrosis. Meanwhile, SNX11, a close homologue of SNX10, was found to be able to inhibit SNX10-induced vacuolation. We recently reported the crystal structure of SNX11 and proposed a novel extended PX domain.1 Our study on SNX10 confirmed this finding. We also observed different specificities for phosphoinositide lipids between SNX10 and SNX11. These findings will further our understanding on SNXs’ roles in endosomal trafficking.