Genetic isolation of transport signals directing cell surface expression

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.

Cite this article

Shikano, S., Coblitz, B., Sun, H. et al. Genetic isolation of transport signals directing cell surface expression. Nat Cell Biol 7, 985–992 (2005). https://doi.org/10.1038/ncb1297

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