Receptor-mediated protein transport in the early secretory pathway

2007 ◽  
Vol 32 (8) ◽  
pp. 381-388 ◽  
Author(s):  
Andrea C. Baines ◽  
Bin Zhang
Keyword(s):  
Secretory Pathway ◽  
Protein Transport ◽  
Early Secretory Pathway

scholarly journals A stress assembly that confers cell viability by preserving ERES components during amino-acid starvation

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Margarita Zacharogianni ◽  
Angelica Aguilera-Gomez ◽  
Tineke Veenendaal ◽  
Jan Smout ◽  
Catherine Rabouille
Keyword(s):  
Amino Acid ◽  
Cell Viability ◽  
Secretory Pathway ◽  
Protein Transport ◽  
Liquid Droplet ◽  
Protein Translation ◽  
Amino Acid Starvation ◽  
Early Secretory Pathway ◽  
Er Exit Sites ◽  
Nutritional Restriction

Nutritional restriction leads to protein translation attenuation that results in the storage and degradation of free mRNAs in cytoplasmic assemblies. In this study, we show in Drosophila S2 cells that amino-acid starvation also leads to the inhibition of another major anabolic pathway, the protein transport through the secretory pathway, and to the formation of a novel reversible non-membrane bound stress assembly, the Sec body that incorporates components of the ER exit sites. Sec body formation does not depend on membrane traffic in the early secretory pathway, yet requires both Sec23 and Sec24AB. Sec bodies have liquid droplet-like properties, and they act as a protective reservoir for ERES components to rebuild a functional secretory pathway after re-addition of amino-acids acting as a part of a survival mechanism. Taken together, we propose that the formation of these structures is a novel stress response mechanism to provide cell viability during and after nutrient stress.

scholarly journals Casein Kinase I Regulates Membrane Binding by ARF GAP1

2002 ◽  
Vol 13 (8) ◽  
pp. 2559-2570 ◽  
Author(s):  
Sidney Yu ◽  
Michael G. Roth
Keyword(s):  
Amino Acid ◽  
Secretory Pathway ◽  
Protein Transport ◽  
Membrane Binding ◽  
Casein Kinase ◽  
Protein Domain ◽  
Amino Terminal ◽  
Early Secretory Pathway

ARF GAP1, a 415-amino acid GTPase activating protein (GAP) for ADP-ribosylation factor (ARF) contains an amino-terminal 115-amino acid catalytic domain and no other recognizable features. Amino acids 203–334 of ARF GAP1 were sufficient to target a GFP-fusion protein to Golgi membranes in vivo. When overexpressed in COS-1 cells, this protein domain inhibited protein transport between the ER and Golgi and, in vitro, competed with the full-length ARF GAP1 for binding to membranes. Membrane binding by ARF GAP1 in vitro was increased by a factor in cytosol and this increase was inhibited by IC261, an inhibitor selective for casein kinase Iδ (CKIδ), or when cytosol was treated with antibody to CKIδ. The noncatalytic domain of ARF GAP1 was phosphorylated both in vivo and in vitro by CKI. IC261 blocked membrane binding by ARF GAP1 in vivo and inhibited protein transport in the early secretory pathway. Overexpression of a catalytically inactive CKIδ also inhibited the binding of ARF GAP1 to membranes and interfered with protein transport. Thus, a CKI isoform is required for protein traffic through the early secretory pathway and can modulate the amount of ARF GAP1 that can bind to membranes.

Biosynthetic protein transport through the early secretory pathway

1998 ◽  
Vol 109 (5-6) ◽  
pp. 477-486 ◽  
Author(s):  
W. Nickel ◽  
Felix T. Wieland
Keyword(s):  
Secretory Pathway ◽  
Protein Transport ◽  
Early Secretory Pathway

scholarly journals Targeting CCR5 trafficking to inhibit HIV-1 infection

2019 ◽  
Vol 5 (10) ◽  
pp. eaax0821 ◽  
Author(s):  
Gaelle Boncompain ◽  
Floriane Herit ◽  
Sarah Tessier ◽  
Aurianne Lescure ◽  
Elaine Del Nery ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Secretory Pathway ◽  
Protein Transport ◽  
Molecular Level ◽  
High Content Screening ◽  
Differential Protein ◽  
Early Secretory Pathway ◽  
A Cell ◽  
Hiv Entry ◽  
Hiv 1

Using a cell-based assay monitoring differential protein transport in the secretory pathway coupled to high-content screening, we have identified three molecules that specifically reduce the delivery of the major co-receptor for HIV-1, CCR5, to the plasma membrane. They have no effect on the closely related receptors CCR1 and CXCR4. These molecules are also potent in primary macrophages as they markedly decrease HIV entry. At the molecular level, two of these molecules inhibit the critical palmitoylation of CCR5 and thereby block CCR5 in the early secretory pathway. Our results open a clear therapeutics avenue based on trafficking control and demonstrate that preventing HIV infection can be performed at the level of its receptor delivery.

scholarly journals Morphological analysis of protein transport from the ER to Golgi membranes in digitonin-permeabilized cells: role of the P58 containing compartment.

1992 ◽  
Vol 119 (5) ◽  
pp. 1097-1116 ◽  
Author(s):  
H Plutner ◽  
H W Davidson ◽  
J Saraste ◽  
W E Balch
Keyword(s):  
G Protein ◽  
Secretory Pathway ◽  
Protein Transport ◽  
Permeabilized Cells ◽  
Early Secretory Pathway ◽  
Transport Component ◽  
Membrane Bound ◽  
Golgi Network ◽  
Putative Marker

The glycoside digitonin was used to selectively permeabilize the plasma membrane exposing functionally and morphologically intact ER and Golgi compartments. Permeabilized cells efficiently transported vesicular stomatitis virus glycoprotein (VSV-G) through sealed, membrane-bound compartments in an ATP and cytosol dependent fashion. Transport was vectorial. VSV-G protein was first transported to punctate structures which colocalized with p58 (a putative marker for peripheral punctate pre-Golgi intermediates and the cis-Golgi network) before delivery to the medial Golgi compartments containing alpha-1,2-mannosidase II and processing of VSV-G to endoglycosidase H resistant forms. Exit from the ER was inhibited by an antibody recognizing the carboxyl-terminus of VSV-G. In contrast, VSV-G protein colocalized with p58 in the absence of Ca2+ or the presence of an antibody which inhibits the transport component NSF (SEC18). These studies demonstrate that digitonin permeabilized cells can be used to efficiently reconstitute the early secretory pathway in vitro, allowing a direct comparison of the morphological and biochemical events involved in vesicular tafficking, and identifying a key role for the p58 containing compartment in ER to Golgi transport.

scholarly journals A Cell-Specific Transgenic Approach in Xenopus Reveals the Importance of a Functional p24 System for a Secretory Cell

2004 ◽  
Vol 15 (3) ◽  
pp. 1244-1253 ◽  
Author(s):  
Gerrit Bouw ◽  
Rick Van Huizen ◽  
Eric J.R. Jansen ◽  
Gerard J.M. Martens
Keyword(s):  
Secretory Pathway ◽  
Protein Transport ◽  
Transgenic Animal ◽  
Secretory Protein ◽  
Physiological Effect ◽  
Early Secretory Pathway ◽  
Golgi Transport ◽  
Cargo Transport ◽  
Transport Vesicles ◽  
A Cell

The p24α, -β, -γ, and -δ proteins are major multimeric constituents of cycling endoplasmic reticulum-Golgi transport vesicles and are thought to be involved in protein transport through the early secretory pathway. In this study, we targeted transgene overexpression of p24δ2 specifically to the Xenopus intermediate pituitary melanotrope cell that is involved in background adaptation of the animal and produces high levels of its major secretory cargo proopiomelanocortin (POMC). The transgene product effectively displaced the endogenous p24 proteins, resulting in a melanotrope cell p24 system that consisted predominantly of the transgene p24δ2 protein. Despite the severely distorted p24 machinery, the subcellular structures as well as the level of POMC synthesis were normal in these cells. However, the number and pigment content of skin melanophores were reduced, impairing the ability of the transgenic animal to fully adapt to a black background. This physiological effect was likely caused by the affected profile of POMC-derived peptides observed in the transgenic melanotrope cells. Together, our results suggest that in the early secretory pathway an intact p24 system is essential for efficient secretory cargo transport or for supplying cargo carriers with the correct protein machinery to allow proper secretory protein processing.

scholarly journals Suppression of Coatomer Mutants by a New Protein Family with COPI and COPII Binding Motifs in Saccharomyces cerevisiae

2003 ◽  
Vol 14 (8) ◽  
pp. 3097-3113 ◽  
Author(s):  
Thomas Sandmann ◽  
Johannes M. Herrmann ◽  
Jörn Dengjel ◽  
Heinz Schwarz ◽  
Anne Spang
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Trafficking ◽  
Secretory Pathway ◽  
Protein Transport ◽  
Integral Membrane Protein ◽  
Eukaryotic Cell ◽  
Vesicle Formation ◽  
Binding Motifs ◽  
Early Secretory Pathway ◽  
Direct Binding

Protein trafficking is achieved by a bidirectional vesicle flow between the various compartments of the eukaryotic cell. COPII coated vesicles mediate anterograde protein transport from the endoplasmic reticulum to the Golgi apparatus, whereas retrograde Golgi-to-endoplasmic reticulum vesicles use the COPI coat. Inactivation of COPI vesicle formation in conditional sec21 (γ-COP) mutants rapidly blocks transport of certain proteins along the early secretory pathway. We have identified the integral membrane protein Mst27p as a strong suppressor of sec21-3 and ret1-1 mutants. A C-terminal KKXX motif of Mst27p that allows direct binding to the COPI complex is crucial for its suppression ability. Mst27p and its homolog Yar033w (Mst28p) are part of the same complex. Both proteins contain cytoplasmic exposed C termini that have the ability to interact directly with COPI and COPII coat complexes. Site-specific mutations of the COPI binding domain abolished suppression of the sec21 mutants. Our results indicate that overexpression of MST27 provides an increased number of coat binding sites on membranes of the early secretory pathway and thereby promotes vesicle formation. As a consequence, the amount of cargo that can bind COPI might be important for the regulation of the vesicle flow in the early secretory pathway.

scholarly journals Conserved function of ether lipids and sphingolipids in the early secretory pathway

2019 ◽  
Author(s):  
Noemi Jiménez-Rojo ◽  
Manuel D. Leonetti ◽  
Valeria Zoni ◽  
Adai Colom ◽  
Suihan Feng ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
Cell Biology ◽  
Secretory Pathway ◽  
Protein Transport ◽  
Lipid Synthesis ◽  
Chemical Properties ◽  
Ether Lipid ◽  
Ether Lipids ◽  
Early Secretory Pathway ◽  
A Genome

ABSTRACTSphingolipids have been shown to play important roles in physiology and cell biology, but a systematic examination of their functions is lacking. We performed a genome-wide CRISPRi screen in sphingolipid-depleted cells and identified hypersensitive mutants in genes of membrane trafficking and lipid biosynthesis, including ether lipid synthesis. Systematic lipidomic analysis showed a coordinate regulation of ether lipids with sphingolipids, where depletion of one of these lipid types resulted in increases in the other, suggesting an adaptation and functional compensation. Biophysical experiments on model membranes show common properties of these structurally diverse lipids that also share a known function as GPI anchors in different kingdoms of life. Molecular dynamics simulations show a selective enrichment of ether phosphatidylcholine around p24 proteins, which are receptors for the export of GPI-anchored proteins and have been shown to bind a specific sphingomyelin species. Our results support a model of convergent evolution of proteins and lipids, based on their physico-chemical properties, to regulate GPI-anchored protein transport and maintain homeostasis in the early secretory pathway.

Localization of p24 putative cargo receptors in the early secretory pathway depends on the biosynthetic activity of the cell

2001 ◽  
Vol 360 (2) ◽  
pp. 421-429 ◽  
Author(s):  
Roland P. KUIPER ◽  
Gerrit BOUW ◽  
Karel P. C. JANSSEN ◽  
Jutta RÖTTER ◽  
François van HERP ◽  
...  
Keyword(s):  
Subcellular Localization ◽  
Anterior Pituitary ◽  
Secretory Pathway ◽  
Protein Transport ◽  
Pituitary Cells ◽  
Biosynthetic Activity ◽  
Early Secretory Pathway ◽  
Highly Active ◽  
Anterior Pituitary Cells ◽  
P24 Proteins

Members of the p24 family of putative cargo receptors (subdivided into p24-α, −β, −γ and −δ) are localized in the intermediate-and cis-Golgi compartments of the early secretory pathway, and are thought to play an important role in protein transport. In the present study, we wondered what effect increased biosynthetic cell activity with resulting high levels of protein transport would have on the subcellular localization of p24. We examined p24 localization in Xenopus intermediate pituitary melanotrope cells, which in black- and white-adapted animals are biosynthetically highly active and virtually inactive respectively. In addition, p24 localization was studied in Xenopus anterior pituitary cells whose activity is not changed during background adaptation. Using organelle fractionation, we found that in the inactive melanotropes and moderately active anterior pituitary cells of white-adapted animals, the p24-α, −β, −γ and −δ proteins are all located in the Golgi compartment. In the highly active melanotropes, but not in the anterior cells of black-adapted animals, the steady-state distribution of all four p24 members changed towards the intermediate compartment and subdomains of the endoplasmic reticulum (ER), most probably the ER exit sites. In the active melanotropes, the major cargo protein pro-opiomelanocortin was mostly localized to ER subdomains and partially co-localized with the p24 proteins. Furthermore, in the active cells, in vitro blocking of protein biosynthesis by cycloheximide or dispersion of the Golgi complex by brefeldin A led to a redistribution of the p24 proteins, indicating their involvement in ER-to-Golgi protein transport and extensive cycling in the early secretory pathway. We conclude that the subcellular localization of p24 proteins is dynamic and depends on the biosynthetic activity of the cell.

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