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PMID: 20733053 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

SNX27 mediates PDZ-directed sorting from endosomes to the plasma membrane.

The Journal of cell biology ·Vol. 190 ·No. 4 ·2010-08-23 ·Pages 565-74

Lauffer BE, Melero C, Temkin P, Lei C, Hong W, Kortemme T, von Zastrow M

Abstract

Postsynaptic density 95/discs large/zonus occludens-1 (PDZ) domain-interacting motifs, in addition to their well-established roles in protein scaffolding at the cell surface, are proposed to act as cis-acting determinants directing the molecular sorting of transmembrane cargo from endosomes to the plasma membrane. This hypothesis requires the existence of a specific trans-acting PDZ protein that mediates the proposed sorting operation in the endosome membrane. Here, we show that sorting nexin 27 (SNX27) is required for efficient PDZ-directed recycling of the beta(2)-adrenoreceptor (beta(2)AR) from early endosomes. SNX27 mediates this sorting function when expressed at endogenous levels, and its recycling activity requires both PDZ domain-dependent recognition of the beta(2)AR cytoplasmic tail and Phox homology (PX) domain-dependent association with the endosome membrane. These results identify a discrete role of SNX27 in PDZ-directed recycling of a physiologically important signaling receptor, and extend the concept of cargo-specific molecular sorting in the recycling pathway.

MeSH Terms
Amino Acid Sequence Animals Cell Line Cell Membrane/metabolism Endosomes/metabolism Humans Molecular Sequence Data PDZ Domains Phosphoproteins/genetics,metabolism Protein Transport/physiology RNA, Small Interfering/genetics,metabolism Receptors, Adrenergic, beta-2/genetics,metabolism Recombinant Fusion Proteins/genetics,metabolism Sequence Alignment Sodium-Hydrogen Exchangers/genetics,metabolism Sorting Nexins Vesicular Transport Proteins/genetics,metabolism
Chemicals
Phosphoproteins RNA, Small Interfering Receptors, Adrenergic, beta-2 Recombinant Fusion Proteins SNX27 protein, human Sodium-Hydrogen Exchangers Sorting Nexins Vesicular Transport Proteins sodium-hydrogen exchanger regulatory factor
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Lauffer Benjamin E L
Program in Pharmaceutical Sciences and Pharmacogenomics, University of California-San Francisco, San Francisco, CA 94158, USA.
Melero Cristina
Temkin Paul
Lei Cai
Hong Wanjin
Kortemme Tanja
von Zastrow Mark
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.201004060
Published
2010-08-23
Pages
565-74
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2928020
Subset
IM
Grants
NIDA NIH HHS · R37 DA010711 · United States
NIDA NIH HHS · DA012864 · United States
NIDA NIH HHS · R29 DA010711 · United States
NIDA NIH HHS · R01 DA012864 · United States
NIDA NIH HHS · R01 DA010711 · United States
NEI NIH HHS · PN2 EY016546 · United States
NIDA NIH HHS · DA010711 · United States
External Links
PubMed source DOI: 10.1083/jcb.201004060 PMC Full Text View journal details
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