Letter | Published:

Genetic isolation of transport signals directing cell surface expression

Nature Cell Biology volume 7, pages 985992 (2005) | Download Citation

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Abstract

Membrane proteins represent approximately 30% of the proteome in both prokaryotes and eukaryotes1. The spatial localization of membrane-bound proteins is often determined by specific sequence motifs2 that may be regulated in response to physiological changes, such as protein interactions3 and receptor signalling4. Identification of signalling motifs is therefore important for understanding membrane protein expression, function and transport mechanisms. We report a genetic isolation of novel motifs that confer surface expression. Further characterization showed that SWTY, one class of these isolated motifs with homology to previously reported forward transport motifs5, has the ability to both override the RKR endoplasmic reticulum localization signal and potentiate steady-state surface expression. The genetically isolated SWTY motif is functionally interchangeable with a known motif in cardiac potassium channels and an identified motif in an HIV coreceptor, and operates by recruiting 14-3-3 proteins. This study expands the repertoire of and enables a screening method for membrane trafficking signals.

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Acknowledgements

We thank L. Jan for providing Kir2.1 and Kir6.2 cDNAs, S. Goldstein for KCNK3 cDNA, H. Fu for providing 14-3-3 constructs and many insightful discussions, R. Doms for GPR15 cDNA, M. Spieker and R. Sheng for helping with DNA recovery and sequencing, and the members of the Li laboratory and C. Montell and C. Machamer for helpful comments on this manuscript. We are indebted to S. Goldstein for his invaluable advice on this manuscript. The work is supported by grants from the National Institutes of Health (GM70959 and NS33324 to M.L.); pre-doctoral (to B.C.) and postdoctoral (to H.S.) fellowship awards from the American Heart Association.

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Affiliations

  1. Department of Neuroscience and High Throughput Biology Center, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA.

    • Sojin Shikano
    • , Brian Coblitz
    • , Haiyan Sun
    •  & Min Li

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Min Li.

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DOI

https://doi.org/10.1038/ncb1297

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