A Specific Endoplasmic Reticulum Export Signal Drives Transport of Stem Cell Factor (Kitl) to the Cell Surface

Paulhe, Frédérique; Imhof, Beat A.; Wehrle-Haller, Bernhard

doi:10.1074/jbc.m407813200

Cited by 26 publications

(31 citation statements)

References 61 publications

(84 reference statements)

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“…Wildtype p22 did not co-localize with the ER-marker protein calnexin (Figure 5E), as would be expected for a protein that utilizes an ER export signal [40], [41]. In contrast, the AXΦASDG construct of p22 exhibited a more diffuse and reticular staining pattern, much of which overlapped with the ER (Figure 5E, inset), suggesting that the mutated residues were either re-localizing the protein to the ER or slowing the trafficking of the protein from the ER.…”

Section: Resultssupporting

confidence: 52%

Inhibition of Cellular Protein Secretion by Norwalk Virus Nonstructural Protein p22 Requires a Mimic of an Endoplasmic Reticulum Export Signal

et al. 2010

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Protein trafficking between the endoplasmic reticulum (ER) and Golgi apparatus is central to cellular homeostasis. ER export signals are utilized by a subset of proteins to rapidly exit the ER by direct uptake into COPII vesicles for transport to the Golgi. Norwalk virus nonstructural protein p22 contains a YXΦESDG motif that mimics a di-acidic ER export signal in both sequence and function. However, unlike normal ER export signals, the ER export signal mimic of p22 is necessary for apparent inhibition of normal COPII vesicle trafficking, which leads to Golgi disassembly and antagonism of Golgi-dependent cellular protein secretion. This is the first reported function for p22. Disassembly of the Golgi apparatus was also observed in cells replicating Norwalk virus, which may contribute to pathogenesis by interfering with cellular processes that are dependent on an intact secretory pathway. These results indicate that the ER export signal mimic is critical to the antagonistic function of p22, shown herein to be a novel antagonist of ER/Golgi trafficking. This unique and well-conserved human norovirus motif is therefore an appealing target for antiviral drug development.

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Section: Resultssupporting

confidence: 52%

Inhibition of Cellular Protein Secretion by Norwalk Virus Nonstructural Protein p22 Requires a Mimic of an Endoplasmic Reticulum Export Signal

et al. 2010

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“…On the other hand, a valine residue at the very C-terminal position of the cytoplasmic tail of transmembrane proteins, reported to function as a forward transport signal by binding to specific Sec24p isoforms [31,33] or to the Golgi matrix proteins GRASP65 and GRASP55 [87], is highly over represented with 145 of 984 human transmembrane proteins and 114 of 782 mouse transmembrane proteins possessing a terminal valine, representing frequencies about 170% greater than randomly expected (Table 2). However, the presence of a C-terminal valine does not guarantee rapid ER egress.…”

Section: Resultsmentioning

confidence: 99%

The B7-1 Cytoplasmic Tail Enhances Intracellular Transport and Mammalian Cell Surface Display of Chimeric Proteins in the Absence of a Linear ER Export Motif

Lin

Chen

et al. 2013

PLoS ONE

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Membrane-tethered proteins (mammalian surface display) are increasingly being used for novel therapeutic and biotechnology applications. Maximizing surface expression of chimeric proteins on mammalian cells is important for these applications. We show that the cytoplasmic domain from the B7-1 antigen, a commonly used element for mammalian surface display, can enhance the intracellular transport and surface display of chimeric proteins in a Sar1 and Rab1 dependent fashion. However, mutational, alanine scanning and deletion analysis demonstrate the absence of linear ER export motifs in the B7 cytoplasmic domain. Rather, efficient intracellular transport correlated with the presence of predicted secondary structure in the cytoplasmic tail. Examination of the cytoplasmic domains of 984 human and 782 mouse type I transmembrane proteins revealed that many previously identified ER export motifs are rarely found in the cytoplasmic tail of type I transmembrane proteins. Our results suggest that efficient intracellular transport of B7 chimeric proteins is associated with the structure rather than to the presence of a linear ER export motif in the cytoplasmic tail, and indicate that short (less than ~ 10-20 amino acids) and unstructured cytoplasmic tails should be avoided to express high levels of chimeric proteins on mammalian cells.

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“…The C-terminal valine is essential for ER export of HLA-F. Other immune system molecules such as CD8␣ (30), pro-TGF␣ (39,40), MTI-MPP (40), in addition to other proteins (31,41,42) also require a C-terminal valine to be captured into COPII vesicles for ER-to-Golgi transport. Because C-terminal valine residues are found in ϳ10% of human type I membrane proteins this feature may provide a general mechanism for ER export (33).…”

Section: Discussionmentioning

confidence: 99%

Selective Export of HLA-F by Its Cytoplasmic Tail

Boyle

Gillingham

Munro

et al. 2006

The Journal of Immunology

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MHC class I molecules exit the endoplasmic reticulum (ER) by an unknown mechanism. Although a selective export mechanism has been proposed for the anterograde transport of class I, a motif responsible for export has never been identified. Although classical class I molecules lacking their cytoplasmic tail are expressed on the cell surface, we found that HLA-F was entirely dependent on its cytoplasmic tail for export from the ER. Two known export motifs were recognizable in HLA-F. A C-terminal valine residue functioned in ER export and interacted with coat complex (COP)II, while an RxR motif also played an important role in anterograde transport and bound to 14-3-3 proteins. This divergent trafficking of HLA-F implicates an alternative function for HLA-F, independent of loading with peptides in the ER.

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A Specific Endoplasmic Reticulum Export Signal Drives Transport of Stem Cell Factor (Kitl) to the Cell Surface

Cited by 26 publications

References 61 publications

Inhibition of Cellular Protein Secretion by Norwalk Virus Nonstructural Protein p22 Requires a Mimic of an Endoplasmic Reticulum Export Signal

Inhibition of Cellular Protein Secretion by Norwalk Virus Nonstructural Protein p22 Requires a Mimic of an Endoplasmic Reticulum Export Signal

The B7-1 Cytoplasmic Tail Enhances Intracellular Transport and Mammalian Cell Surface Display of Chimeric Proteins in the Absence of a Linear ER Export Motif

Selective Export of HLA-F by Its Cytoplasmic Tail

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