SNX27 is important for postnatal development in mice

Abstract

Sorting nexin 27 (SNX27) is a newly identified member of the SNX family that is characterized by the presence of an evolutionarily conserved Phox (PX) domain. SNX27 is targeted to the early endosome by the interaction of its PX domain with phosphatidylinositol-3-phosphate (PI(3)P). In order to study the physiological function of SNX27, we have produced mice homozygous for a null mutation of SNX27 by gene targeting. Generally, SNX27-/- mice displayed severe growth retardation and all died within 3 weeks of age. Retardation of growth was seen in most organs as they are all smaller than those in the wild-type littermates. Furthermore, through yeast two-hybrid screening, we identified a novel SNX27 interacting protein, the N-methyl-D-aspartate (NMDA) receptor 2c (NR2c). This interaction was mediated by the binding of the PDZ domain of SNX27 with the C-terminal PDZ-binding motif of NR2c. The level of NR2c was found to be increased in SNX27-/- mice, implying that SNX27 may function to regulate endosomal sorting of NR2c for lysosomal degradation. These results suggest that SNX27 may regulate endosomal sorting of membrane proteins containing PDZ-binding motif and its absence may alter the trafficking of these proteins, leading to survival and organ developmental defects in mice.