Sorting nexin 27 (SNX27) is a 62-kDa protein localized to early endosomes and 
known to regulate the intracellular trafficking of ion channels and receptors. 
In addition to a PX domain, SNX27 is the only sorting family member that 
contains a PDZ domain. To identify novel SNX27-PDZ binding partners, we 
performed a proteomic screen in mouse principal kidney cortical collecting duct 
cells using a GST-SNX27 fusion construct as bait. We found that β-Pix 
(p21-activated kinase-interactive exchange factor), a guanine nucleotide 
exchange factor for the Rho family of small GTPases known to regulate cell 
motility directly interacted with SNX27. The association of β-Pix and SNX27 is 
specific for β-Pix isoforms terminating in the type-1 PDZ binding motif (ETNL). 
In the same screen we also identified Git1/2 as a potential SNX27 interacting 
protein. The interaction between SNX27 and Git1/2 is indirect and mediated by 
β-Pix. Furthermore, we show recruitment of the β-Pix·Git complex to endosomal 
sites in a SNX27-dependent manner. Finally, migration assays revealed that 
depletion of SNX27 from HeLa and mouse principal kidney cortical collecting duct 
cells significantly decreases cell motility. We propose a model by which SNX27 
regulates trafficking of β-Pix to focal adhesions and thereby influences cell 
motility.