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  current news   Press   selected story    
     
  7th March 2011  
 

Deficiency of Sorting Nexin 27 (SNX27) Leads to Growth Retardation and Elevated Levels of N-methyl-D-aspartate (NMDA) Receptor 2C (NR2C).

 
 




Authors
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,
Singapore 117597.

ˆ - These authors contributed equally to this work.

# - Corresponding author.

Published in Mol Cell Biol. 2011 Feb 7. [Epub ahead of print]

Abstract

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.

 

 
 

 
 


Figure Legend: SNX27 deficiency caused growth retardation and reduced survival during embryonic development and severe postnatal growth retardation and lethality of newborn pups.
(A) a. Among 152 newborn pups, the ratio of SNX27-/- mice is only 16%, lower than the expected 25%, indicating the loss of some of SNX27-/- embryos during development. Among 152 newborn pups: 25 are SNX27-/-, 44 are SNX27+/+, and 83 are SNX27+/-. b. Newborn SNX27-/- mice are smaller in size compared with the wildtype pups in the same litter. c. Body weight comparison among newborn SNX27+/+, +/- and -/- mice, showing that SNX27-/- mice are significantly lighter. n=10.

(B) The body weights during postnatal growth of SNX27-/- and SNX27+/+ pups were plotted as a function of time, showing severe delayed growth in body weight gain of SNX27-/- pups. All SNX27-/- mice died before weaning.

(C) The image of SNX27-/- and wild-type mouse from the same litter at 10 days after birth (left image). The image of SNX27-/- and wild-type mouse from the same litter at 20 days after birth, showing the dramatically reduced sizes (right image).

(D) The image of some major organs from SNX27-/- and wild-type mouse at 10 days after birth, showing reduced sizes of multiple organs of SNX27-/- mouse.

For more information on Wanjin HONG’s laboratory, please click here.