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PMID: 21300787 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Deficiency of sorting nexin 27 (SNX27) leads to growth retardation and elevated levels of N-methyl-D-aspartate receptor 2C (NR2C).

Molecular and cellular biology ·Vol. 31 ·No. 8 ·2011-04-00 ·Pages 1734-47

Cai L, Loo LS, Atlashkin V, Hanson BJ, Hong W

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 the 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 a PDZ-binding motif, and its absence may alter the trafficking of these proteins, leading to growth and survival defects.

MeSH Terms
Amino Acid Sequence Animals Cell Line Conserved Sequence Evolution, Molecular Humans Mice Mice, Knockout Molecular Sequence Data Phosphatidylinositol 3-Kinases/metabolism Receptors, N-Methyl-D-Aspartate/chemistry,genetics,metabolism Sequence Alignment Sorting Nexins/deficiency,genetics,metabolism
Chemicals
NR2C NMDA receptor Receptors, N-Methyl-D-Aspartate SNX27 protein, human Snx27 protein, mouse Sorting Nexins Phosphatidylinositol 3-Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Cai Lei
Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Singapore.
Loo Li Shen
Atlashkin Vadim
Hanson Brendon J
Hong Wanjin
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
1098-5549
DOI
10.1128/MCB.01044-10
Published
2011-04-00
Epub
2011-00-07
Pages
1734-47
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC3126336
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.01044-10 PMC Full Text View journal details
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