Lei Cai1,ˆ, Li Shen Loo1,ˆ,#, Vadim Atlashkin1, Brendon J Hanson2 and Wanjin Hong11,3.
1 - Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673.
2 - Defence Medical and Environmental Research Institute, DSO National Laboratories, 27 Medical Dr., Singapore 117510.
3 - Department of Biochemistry, National University of Singapore, 8 Medical Drive,
ˆ - These authors contributed equally to this work.
# - Corresponding author.
Published in Mol Cell Biol. 2011 Feb 7. [Epub ahead of print]
Phox (PX) domain-containing sorting nexins (SNXs) are emerging as important regulators of endocytic trafficking. Sorting nexin 27 (SNX27) is unique as it contains a PDZ (Psd-95/Dlg/ZO1) domain. We show here that SNX27 is primarily targeted to the early endosome by interaction of its PX domain with PtdIns(3)P. Although targeted ablation of SNX27 gene in mice did not significantly affect growth and survival during embryonic development, SNX27 plays an essential role in postnatal growth and survival. N-methyl-D-aspartate (NMDA) receptor 2C (NR2C) was identified as a novel SNX27-interacting protein and this interaction is mediated by the PDZ domain of SNX27 and the C-terminal PDZ-binding motif of NR2C. Increased NR2C expression levels, together with impaired NR2C endocytosis in SNX27(-/-) neurons, indicate that SNX27 may function to regulate endocytosis and/or endosomal sorting of NR2C. This is consistent with a role of SNX27 as a general regulator for sorting of membrane proteins containing PDZ-binding motif and its absence may alter the trafficking of these proteins, leading to growth and survival defects.