Protein Sorting Receptors in the Early Secretory Pathway

Dancourt, Julia; Barlowe, Charles

doi:10.1146/annurev-biochem-061608-091319

Cited by 277 publications

(280 citation statements)

References 151 publications

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“…(D) ER exit: The natively folded protein is released from the CNX/CRT cycle and transported to its destination. In the early secretory pathway, lectins (ERGIC53, VIP36, and VIPL) support the sorting or trafficking of glycosylated proteins from the ER to the Golgi (Kamiya et al 2008;Dancourt and Barlowe 2010). "[ ]" indicates that there are several possibilities for N-glycan formation.…”

Section: Translation Of Er-targeted Proteinsmentioning

confidence: 99%

Protein Folding and Quality Control in the ER

Araki

Nagata

2011

Cold Spring Harbor Perspectives in Biology

317

285

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The endoplasmic reticulum (ER) uses an elaborate surveillance system called the ER quality control (ERQC) system. The ERQC facilitates folding and modification of secretory and membrane proteins and eliminates terminally misfolded polypeptides through ER-associated degradation (ERAD) or autophagic degradation. This mechanism of ER protein surveillance is closely linked to redox and calcium homeostasis in the ER, whose balance is presumed to be regulated by a specific cellular compartment. The potential to modulate proteostasis and metabolism with chemical compounds or targeted siRNAs may offer an ideal option for the treatment of disease.

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Section: Translation Of Er-targeted Proteinsmentioning

confidence: 99%

Protein Folding and Quality Control in the ER

Araki

Nagata

2011

Cold Spring Harbor Perspectives in Biology

317

285

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“…Instead, multiple signals seem to drive selective capture, meaning the COPII coat must recognize various signals employed by structurally diverse cargoes. Such signals range from simple acidic peptides (Malkus et al 2002) to folded epitopes and can act either by interacting directly with the COPII coat or by binding to a cargo adaptor that links them to the coat indirectly (Figure 4) (Dancourt and Barlowe 2010).…”

Section: Transport From the Er: Sculpting And Populating A Copii Vesiclementioning

confidence: 99%

“…Some cargoes, by topology or preference, do not interact directly with Sec24 but instead use adaptor/receptor proteins to link them to the coat indirectly (Dancourt and Barlowe 2010). Some of these adaptors likely function as canonical receptors, binding to their ligands in one compartment and simultaneously interacting with Sec24 to couple cargo with coat, then releasing their ligand in another compartment, perhaps as the result of a change in ionic strength or pH of the acceptor organelle (Figure 3).…”

Section: Transport From the Er: Sculpting And Populating A Copii Vesiclementioning

confidence: 99%

Secretory Protein Biogenesis and Traffic in the Early Secretory Pathway

2013

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The secretory pathway is responsible for the synthesis, folding, and delivery of a diverse array of cellular proteins. Secretory protein synthesis begins in the endoplasmic reticulum (ER), which is charged with the tasks of correctly integrating nascent proteins and ensuring correct post-translational modification and folding. Once ready for forward traffic, proteins are captured into ER-derived transport vesicles that form through the action of the COPII coat. COPII-coated vesicles are delivered to the early Golgi via distinct tethering and fusion machineries. Escaped ER residents and other cycling transport machinery components are returned to the ER via COPI-coated vesicles, which undergo similar tethering and fusion reactions. Ultimately, organelle structure, function, and cell homeostasis are maintained by modulating protein and lipid flux through the early secretory pathway. In the last decade, structural and mechanistic studies have added greatly to the strong foundation of yeast genetics on which this field was built. Here we discuss the key players that mediate secretory protein biogenesis and trafficking, highlighting recent advances that have deepened our understanding of the complexity of this conserved and essential process. TABLE OF CONTENTS Abstract 383Introduction 384

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“…Anterograde trafficking signals are important mechanisms to facilitate protein movement from the ER to the Golgi apparatus (48,49). Luminal signals are bound by transmembrane receptors in the ER.…”

Section: Discussionmentioning

confidence: 99%

Cytoplasmic Domain of P-selectin Glycoprotein Ligand-1 Facilitates Dimerization and Export from the Endoplasmic Reticulum

Miner¹,

Shao²,

Wang³

et al. 2011

Journal of Biological Chemistry

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P-selectin glycoprotein ligand-1 (PSGL-1) is a homodimeric transmembrane mucin on leukocytes. During inflammation, reversible interactions of PSGL-1 with selectins mediate leukocyte rolling on vascular surfaces. The transmembrane domain of PSGL-1 is required for dimerization, and the cytoplasmic domain propagates signals that activate ␤ 2 integrins to slow rolling on integrin ligands. Leukocytes from knock-in "⌬CD" mice express a truncated PSGL-1 that lacks the cytoplasmic domain. Unexpectedly, they have 10-fold less PSGL-1 on their surfaces than WT leukocytes. Using glycosidases, proteases, Western blotting, confocal microscopy, cell-surface cross-linking, FRET, and pulse-chase metabolic labeling, we demonstrate that deleting the cytoplasmic domain impaired dimerization and delayed export of PSGL-1 from the endoplasmic reticulum (ER), markedly increasing a monomeric precursor in the ER and decreasing mature PSGL-1 on the cell surface. A monomeric full-length PSGL-1 made by substituting the transmembrane domain with that of CD43 exited the ER normally, revealing that dimerization was not required for ER export. Thus, the transmembrane and cytoplasmic domains cooperate to promote dimerization of PSGL-1. Furthermore, the cytoplasmic domain provides a key signal to export precursors of PSGL-1 from the ER to the Golgi apparatus en route to the cell surface.During inflammation, reversible interactions of selectins with their glycosylated ligands mediate leukocyte rolling on vascular surfaces (1). Cooperative signaling upon engagement of selectin ligands and chemokine receptors causes rolling leukocytes to decelerate and arrest through interactions of integrin ␣ L ␤ 2 on leukocytes with intercellular adhesion molecule-1 (ICAM-1) 4 on endothelial cells. Leukocytes then use integrins to migrate across blood vessels in response to chemokine gradients or other signals (2). P-selectin is expressed on activated endothelial cells and platelets; E-selectin is expressed on activated endothelial cells, and L-selectin is expressed on leukocytes (1). Each selectin mediates leukocyte rolling by interacting with a subset of membrane glycoproteins that must be appropriately glycosylated and, for ligands binding to P-and L-selectin, sulfated. P-selectin glycoprotein ligand-1 (PSGL-1) is a homodimeric, type I transmembrane mucin (1, 3, 4). It is the dominant ligand for P-and L-selectin on leukocytes (5-8), and it cooperates with other ligands to mediate rolling on E-selectin (9 -11). Dimerization of PSGL-1 enhances rolling on P-selectin (12). The subunits of the PSGL-1 homodimer are linked by a disulfide bond just outside the plasma membrane (13). Each extracellular domain has multiple Ser/Thr-linked O-glycans that cause it to adopt a highly extended conformation (14). PSGL-1 is localized on the tips of leukocyte microvilli (5) and has affinity for cholesterol-rich membrane domains or lipid rafts (15). It moves to the uropods as cells polarize after chemokine stimulation (16,17).The sequences of the transmembrane and cytoplasmic domai...

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Protein Sorting Receptors in the Early Secretory Pathway

Cited by 277 publications

References 151 publications

Protein Folding and Quality Control in the ER

Protein Folding and Quality Control in the ER

Secretory Protein Biogenesis and Traffic in the Early Secretory Pathway

Cytoplasmic Domain of P-selectin Glycoprotein Ligand-1 Facilitates Dimerization and Export from the Endoplasmic Reticulum

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