Analysis of the retention signals of two resident luminal endoplasmic reticulum proteins by in vitro mutagenesis.

Haugejorden, S. M.; Srinivasan, Mythili; Green, M

doi:10.1016/s0021-9258(18)38074-8

Cited by 49 publications

(12 citation statements)

References 14 publications

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“…Not surprisingly then, surface expression can be detected by flow cytometry and is *25% of wt at 9 h postinfection (not shown). This leak-through of proteins containing a retention sequence has been previously demonstrated, and was suggested to be a characteristic of the individual protein or of different cell types used for expression (35,36). This molecule is presented as well as wt HA (Fig.…”

Section: Methodssupporting

confidence: 62%

Presentation of newly synthesized glycoproteins to CD4+ T lymphocytes. An analysis using influenza hemagglutinin transport mutants.

Kittlesen

Brown

Braciale

et al. 1993

The Journal of Experimental Medicine

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SulnmaryHuman lymphoblastoid cells transiently expressing the hemagglutinin (HA) glycoprotein of influenza virus are rapidly and efficiently recognized by CD4 + HA-specific T lymphocytes. This endogenous presentation pathway is sensitive to chloroquine and is therefore likely related to the classical class II major histocompatibility complex (MHC) exogenous pathway of antigen presentation. In this study we have examined a series of transport-defective HA mutants. We correlate the intracellular fate of the native antigen with its presentation characteristics. We have found that the native antigen must enter the secretory pathway since a cytosolic form is not presented. However, surface expression and normal trafficking through the Golgi apparatus are not required for efficient presentation. Instead, escape of native antigen from the endoplasmic reticulum appears to be both necessary and sufficient for gaining access to a compartment where antigen is processed and binds class II MHC molecules.

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Section: Methodssupporting

confidence: 62%

Presentation of newly synthesized glycoproteins to CD4+ T lymphocytes. An analysis using influenza hemagglutinin transport mutants.

Kittlesen

Brown

Braciale

et al. 1993

The Journal of Experimental Medicine

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“…These re-ing that the coexpression of PDI-KDEL overcomes the cellular retention of this protein. sults confirm those published previously [12] and demonstrate that the removal of the KDEL sequence from PDI results in secretion of PDI. These results also show that PDI is a multifunctional protein that is involved in the the endogenous PDI was not cosecreted with the recombiisomerization of disulphide bonds during protein folding nant PDI, indicating that the overexpression of PDIand functions as a subunit for both prolyl4-hydroxylase KDEL does not result in a general breakdown of the and microsomal triglyceride transfer protein [14,15].…”

supporting

confidence: 91%

Quality control in the endoplasmic reticulum

Bottomley¹,

Batten²,

Lumb

et al. 2001

Current Biology

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Quality control within the endoplasmic reticulum (ER) is thought to be mediated by the interaction of a folding protein with one or several resident ER proteins [1]. Protein disulphide isomerase (PDI) is one such ER resident protein that has been previously shown to interact with proteins during their folding and assembly pathways [2, 3]. It has been assumed that, as a consequence of this interaction, unassembled proteins are retained within the ER. Here, we experimentally show that this is indeed the case. We have taken advantage of our previous finding that PDI interacts with procollagen chains early on in their assembly pathway [2] to address the role of this protein in directly retaining unassembled chains within the ER. Our experimental approach involved expressing individual C-propeptide domains from different procollagen chains in mammalian cells and determining the ability of these domains to interact with PDI and to be secreted. The C-propeptide from the proalpha2(I) chain was retained within the cell, where it formed a complex with PDI. Conversely, the C-propeptide from the proalpha1(III) chain did not form a complex with PDI and was secreted. Both domains were secreted, however, from a stable cell line expressing a secreted form of PDI lacking its ER retrieval signal. Hence, we have demonstrated directly that the intracellular retention of one substrate for ER quality control is due to an interaction with PDI.

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“…This is shown by the observation that disruption of Golgi or enhanced ER retention due to cellular stress leads to decreased localization of PDI in the membrane fraction of macrophages (Santos et al, 2009) or reduced extracellular PDI secretion in hepatocytes (Terada et al, 1995), respectively. Because ER residence and retrograde transport of PDI from the Golgi is dependent on its interaction via the KDEL sequence, mutation or deletion of the KDEL sequence enhances PDI secretion in COS cells (Haugejorden et al, 1991). It is therefore surprising that PDI with an intact KDEL sequence was constitutively secreted from hepatocytes (Terada et al, 1995).…”

Section: Cells Referencementioning

confidence: 99%

Pathophysiological roles of cell surface and extracellular protein disulfide isomerase and their molecular mechanisms

Chiu

Chen

et al. 2021

British J Pharmacology

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Protein disulfide isomerase (PDI) is the prototypic member of the thiol isomerase family that catalyses disulfide bond rearrangement. Initially identified in the endoplasmic reticulum as folding catalysts, PDI and other members in its family have also been widely reported to reside on the cell surface and in the extracellular matrix. Although how PDI is exported and retained on the cell surface remains a subject of debate, this unique pool of PDI is developing into an important mechanism underlying the redox regulation of protein sulfhydryls that are critical for the cellular activities under various disease conditions. This review aims to provide an overview of the pathophysiological roles of surface and extracellular PDI and their underlying molecular mechanisms.Understanding the involvement of extracellular PDI in these diseases will advance our knowledge in the molecular aetiology to facilitate the development of novel pharmacological strategies by specifically targeting PDI in extracellular compartments.

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Analysis of the retention signals of two resident luminal endoplasmic reticulum proteins by in vitro mutagenesis.

Cited by 49 publications

References 14 publications

Presentation of newly synthesized glycoproteins to CD4+ T lymphocytes. An analysis using influenza hemagglutinin transport mutants.

Presentation of newly synthesized glycoproteins to CD4+ T lymphocytes. An analysis using influenza hemagglutinin transport mutants.

Quality control in the endoplasmic reticulum

Pathophysiological roles of cell surface and extracellular protein disulfide isomerase and their molecular mechanisms

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