Cell-type-specific and selectively induced expression of members of the p24 family of putative cargo receptors

2002 ◽  
Vol 115 (5) ◽  
pp. 1049-1058 ◽  
Author(s):  
Jutta Rötter ◽  
Roland P. Kuiper ◽  
Gerrit Bouw ◽  
Gerard J. M. Martens
Keyword(s):  
Secretory Pathway ◽  
Protein Transport ◽  
Type I ◽  
Pituitary Cells ◽  
Cell Type ◽  
Biosynthetic Activity ◽  
Highly Active ◽  
Transport Vesicles ◽  
Cell Type Specific ◽  
P24 Proteins

Members of the p24 family of type I transmembrane proteins are highly abundant in transport vesicles and are thought to be involved in selective protein transport between the endoplasmic reticulum and the Golgi complex. The p24 proteins have been grouped into four subfamilies (α, β,γ, and δ) and appear to assemble into tetrameric complexes that contain only one representative from each subfamily. Here we molecularly dissected the p24 family in a single cell type, namely in the intermediate pituitary melanotrope cells of the amphibian Xenopus laevis. The biosynthetic activity of these cells for production of their major cargo protein proopiomelanocortin (POMC) can be physiologically manipulated via the process of background adaptation (∼30-fold induction, with highly active cells in black toads and virtually inactive cells in white animals). Extensive cDNA library screening revealed the identity of six p24 proteins expressed in the Xenopus melanotrope cells, namely one member of the p24α(α3), one of the p24β (β1), two of the p24γ (γ2, γ3) and two of the p24δ (δ1, δ2) subfamily. Two other Xenopus p24 proteins, Xp24α2 and-γ1, were not expressed in the melanotrope cells, pointing to cell-type specific p24 expression. Of the six melanotrope p24 proteins, the expression of four (Xp24α3, -β1,-γ3 and -δ2) was 20- to 30-fold induced in active versus inactive melanotropes, whereas that of the other two members(Xp24γ2 and -δ1) had not or only slightly increased. The four proteins were induced only in the intermediate melanotrope cells and not in the anterior pituitary cells, and displayed similar overall tissue distributions that differed from those of Xp24γ1,-γ2 and -δ1. Together, our results reveal that p24 expression can be cell-type specific and selectively induced, and suggest that in Xenopus melanotrope cells anα 3/β1/γ3/δ2p24 complex is involved in POMC transport through the early stages of the 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.

scholarly journals Differential Induction of Two p24δ Putative Cargo Receptors upon Activation of a Prohormoneproducing Cell

2000 ◽  
Vol 11 (1) ◽  
pp. 131-140 ◽  
Author(s):  
Roland P. Kuiper ◽  
Hans R. Waterham ◽  
Jutta Rötter ◽  
Gerrit Bouw ◽  
Gerard J. M. Martens
Keyword(s):  
Secretory Pathway ◽  
Protein Transport ◽  
Fold Increase ◽  
Type I ◽  
Black Background ◽  
Background Adaptation ◽  
Cargo Transport ◽  
Transport Vesicles ◽  
Identification And Characterization

The p24 family consists of type I transmembrane proteins that are present abundantly in transport vesicles, may play a role in endoplasmic reticulum-to-Golgi cargo transport, and have been classified into subfamilies named p24α, -β, -γ, and -δ. We previously identified a member of the p24δ subfamily that is coordinately expressed with the prohormone proopiomelanocortin (POMC) in the melanotrope cells of the intermediate pituitary during black background adaptation of the amphibian Xenopus laevis(∼30-fold increase in POMC mRNA). In this study, we report on the characterization of this p24δ member (Xp24δ2) and on the identification and characterization of a second member (Xp24δ1) that is also expressed in the melanotrope cells and that has 66% amino acid sequence identity to Xp24δ2. The two p24δ members are ubiquitously expressed, but Xp24δ2 is neuroendocrine enriched. During black background adaptation, the amount of the Xp24δ2 protein in the intermediate pituitary was increased ∼25 times, whereas Xp24δ1 protein expression was increased only 2.5 times. Furthermore, the level of Xp24δ2 mRNA was ∼5-fold higher in the melanotrope cells of black-adapted animals than in those of white-adapted animals, whereas Xp24δ1 mRNA expression was not induced. Therefore, the expression of Xp24δ2specifically correlates with the expression of POMC. Together, our findings suggest that p24δ proteins have a role in selective protein transport in the secretory pathway.

scholarly journals Conserved gammaherpesvirus protein kinase counters the antiviral effects of myeloid cell specific STAT1 expression to promote the establishment of splenic B cell latency.

2021 ◽  
Author(s):  
P. A. Sylvester ◽  
C. N. Jondle ◽  
K. P. Stoltz ◽  
J. Lanham ◽  
B. N. Dittel ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
Protein Kinase ◽  
B Cell ◽  
Latent Reservoir ◽  
Type I ◽  
B Cell Differentiation ◽  
Cell Type ◽  
Antiviral Effects ◽  
Cell Type Specific

Gammaherpesviruses establish life-long infections and are associated with B cell lymphomas. Murine gammaherpesvirus-68 (MHV68) infects epithelial and myeloid cells during acute infection, with subsequent passage of the virus to B cells, where physiological B cell differentiation is usurped to ensure the establishment of chronic latent reservoir. Interferons (IFNs) represent a major antiviral defense system that engages transcriptional factor STAT1 to attenuate diverse acute and chronic viral infections, including those of gammaherpesviruses. Correspondingly, global deficiency of type I or type II IFN signaling profoundly increases the pathogenesis of acute and chronic gammaherpesvirus infection, compromises host survival, and impedes mechanistic understanding of cell type-specific role of IFN signaling. Here we demonstrate that myeloid-specific STAT1 deficiency attenuates acute and persistent MHV68 replication in the lungs and suppresses viral reactivation from peritoneal cells, without any effect on the establishment of viral latent reservoir in splenic B cells. All gammaherpesviruses encode a conserved protein kinase that antagonizes type I IFN signaling in vitro. Here, we show that myeloid-specific STAT1 deficiency rescues the attenuated splenic latent reservoir of kinase null MHV68 mutant. However, despite having gained access to splenic B cells, protein kinase null MHV68 mutant fails to drive B cell differentiation. Thus, while myeloid-intrinsic STAT1 expression must be counteracted by the gammaherpesvirus protein kinase to facilitate viral passage to splenic B cells, expression of the viral protein kinase continues to be required to promote optimal B cell differentiation and viral reactivation, highlighting the multifunctional nature of this conserved viral protein during chronic infection. Importance. IFN signaling is a major antiviral system of the host that suppresses replication of diverse viruses, including acute and chronic gammaherpesvirus infection. STAT1 is a critical member and the primary antiviral effector of IFN signaling pathways. Given the significantly compromised antiviral status of global type I or type II IFN deficiency, unabated gammaherpesvirus replication and pathogenesis hinders understanding of cell type-specific antiviral effects. In this study, a mouse model of myeloid-specific STAT1 deficiency unveiled site-specific antiviral effects of STAT1 in the lungs and peritoneal cavity, but not spleen of chronically infected hosts. Interestingly, expression of a conserved gammaherpesvirus protein kinase was required to counteract the antiviral effects of myeloid-specific STAT1 expression to facilitate latent infection of splenic B cells, revealing a cell-type specific virus-host antagonism during the establishment of chronic gammaherpesvirus infection.

scholarly journals Revisiting the role of IRF3 in inflammation and immunity by conditional and specifically targeted gene ablation in mice

2018 ◽  
Vol 115 (20) ◽  
pp. 5253-5258 ◽  
Author(s):  
Hideyuki Yanai ◽  
Shiho Chiba ◽  
Sho Hangai ◽  
Kohei Kometani ◽  
Asuka Inoue ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cell Types ◽  
Type I ◽  
Type I Ifn ◽  
Cell Type ◽  
Gene Ablation ◽  
Cell Type Specific

IFN regulatory factor 3 (IRF3) is a transcription regulator of cellular responses in many cell types that is known to be essential for innate immunity. To confirm IRF3’s broad role in immunity and to more fully discern its role in various cellular subsets, we engineered Irf3-floxed mice to allow for the cell type-specific ablation of Irf3. Analysis of these mice confirmed the general requirement of IRF3 for the evocation of type I IFN responses in vitro and in vivo. Furthermore, immune cell ontogeny and frequencies of immune cell types were unaffected when Irf3 was selectively inactivated in either T cells or B cells in the mice. Interestingly, in a model of lipopolysaccharide-induced septic shock, selective Irf3 deficiency in myeloid cells led to reduced levels of type I IFN in the sera and increased survival of these mice, indicating the myeloid-specific, pathogenic role of the Toll-like receptor 4–IRF3 type I IFN axis in this model of sepsis. Thus, Irf3-floxed mice can serve as useful tool for further exploring the cell type-specific functions of this transcription factor.

scholarly journals The Potential Role of the ZIKV NS5 Nuclear Spherical-Shell Structures in Cell Type-Specific Host Immune Modulation during ZIKV Infection

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1519 ◽  
Author(s):  
Min Jie Alvin Tan ◽  
Kitti Wing Ki Chan ◽  
Ivan H. W. Ng ◽  
Sean Yao Zu Kong ◽  
Chin Piaw Gwee ◽  
...  
Keyword(s):  
Spherical Shell ◽  
Immune Modulation ◽  
Transcriptional Response ◽  
Type I ◽  
Primary Role ◽  
Structural Protein ◽  
Cell Type ◽  
Zikv Infection ◽  
Cell Type Specific

The Zika virus (ZIKV) non-structural protein 5 (NS5) plays multiple viral and cellular roles during infection, with its primary role in virus RNA replication taking place in the cytoplasm. However, immunofluorescence assay studies have detected the presence of ZIKV NS5 in unique spherical shell-like structures in the nuclei of infected cells, suggesting potentially important cellular roles of ZIKV NS5 in the nucleus. Hence ZIKV NS5′s subcellular distribution and localization must be tightly regulated during ZIKV infection. Both ZIKV NS5 expression or ZIKV infection antagonizes type I interferon signaling, and induces a pro-inflammatory transcriptional response in a cell type-specific manner, but the mechanisms involved and the role of nuclear ZIKV NS5 in these cellular functions has not been elucidated. Intriguingly, these cells originate from the brain and placenta, which are also organs that exhibit a pro-inflammatory signature and are known sites of pathogenesis during ZIKV infection in animal models and humans. Here, we discuss the regulation of the subcellular localization of the ZIKV NS5 protein, and its putative role in the induction of an inflammatory response and the occurrence of pathology in specific organs during ZIKV infection.

A cell type-specific transcriptomic approach to map B cell and monocyte type I interferon-linked pathogenic signatures in Multiple Sclerosis

2019 ◽  
Vol 101 ◽  
pp. 1-16 ◽  
Author(s):  
Martina Severa ◽  
Fabiana Rizzo ◽  
Sundararajan Srinivasan ◽  
Marco Di Dario ◽  
Elena Giacomini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cell ◽  
Type I Interferon ◽  
Type I ◽  
Cell Type ◽  
A Cell ◽  
Cell Type Specific

scholarly journals Cell type-specific transgene expression of the prion protein in Xenopus intermediate pituitary cells

FEBS Journal ◽  
2006 ◽  
Vol 273 (4) ◽  
pp. 847-862 ◽  
Author(s):  
Jos W. G. van Rosmalen ◽  
Gerard J. M. Martens
Keyword(s):  
Prion Protein ◽  
Transgene Expression ◽  
Pituitary Cells ◽  
Cell Type ◽  
Cell Type Specific

Diverse roles for the p24 family of proteins in eukaryotic cells

2012 ◽  
Vol 3 (6) ◽  
pp. 561-570 ◽  
Author(s):  
Irmgard Schuiki ◽  
Allen Volchuk
Keyword(s):  
Coat Protein ◽  
Protein Complex ◽  
Complex I ◽  
Secretory Pathway ◽  
Protein Transport ◽  
Protein Quality ◽  
Eukaryotic Cells ◽  
Type I ◽  
P24 Protein ◽  
Coat Protein Complex

AbstractMembers of the p24 protein family form a highly conserved family of type I transmembrane proteins that are abundant components of the early secretory pathway. Topologically, the proteins have a large luminal domain and a short cytoplasmic domain that allows for targeting to both coat protein complex II and coat protein complex I vesicles, and thus these proteins cycle between the endoplasmic reticulum and Golgi compartments. Several functions have been proposed for these proteins including a role in coat protein complex I vesicle biogenesis, cargo protein selection, organization of intracellular membranes, and protein quality control. Recent studies have added to the list of potential cargo substrates for which p24 function is required for normal transport in the secretory pathway. This review focuses on recent developments in the study of p24 proteins and their requirement for secretory and membrane protein transport in eukaryotic cells.

scholarly journals Differential Expression of Ionic Channels in Rat Anterior Pituitary Cells

2001 ◽  
Vol 15 (7) ◽  
pp. 1222-1236 ◽  
Author(s):  
Fredrick Van Goor ◽  
Dragoslava Zivadinovic ◽  
Stanko S. Stojilkovic
Keyword(s):  
Anterior Pituitary ◽  
Ionic Channels ◽  
K Channel ◽  
Pituitary Cells ◽  
Cell Type ◽  
Expression Levels ◽  
Voltage Gated ◽  
Anterior Pituitary Cells ◽  
Cell Type Specific ◽  
Ca2 Channels

Abstract Secretory anterior pituitary cells are of the same origin, but exhibit cell type-specific patterns of spontaneous intracellular Ca2+ signaling and basal hormone secretion. To understand the underlying ionic mechanisms mediating these differences, we compared the ionic channels expressed in somatotrophs, lactotrophs, and gonadotrophs from randomly cycling female rats under identical cell culture and recording conditions. Our results indicate that a similar group of ionic channels are expressed in each cell type, including transient and sustained voltage-gated Ca2+ channels, tetrodotoxin-sensitive Na+ channels, transient and delayed rectifying K+ channels, and multiple Ca2+-sensitive K+ channel subtypes. However, there were marked differences in the expression levels of some of the ionic channels. Specifically, lactotrophs and somatotrophs exhibited low expression levels of tetrodotoxin-sensitive Na+ channels and high expression levels of the large-conductance, Ca2+-activated K+ channel compared with those observed in gonadotrophs. In addition, functional expression of the transient K+ channel was much higher in lactotrophs and gonadotrophs than in somatotrophs. Finally, the expression of the transient voltage-gated Ca2+ channels was higher in somatotrophs than in lactotrophs and gonadotrophs. These results indicate that there are cell type-specific patterns of ionic channel expression, which may be of physiological significance for the control of Ca2+ homeostasis and secretion in unstimulated and receptor-stimulated anterior pituitary cells.

scholarly journals Cell-Type-Specific Type I Interferon Antagonism Influences Organ Tropism of Murine Coronavirus

2011 ◽  
Vol 85 (19) ◽  
pp. 10058-10068 ◽  
Author(s):  
L. Zhao ◽  
K. M. Rose ◽  
R. Elliott ◽  
N. Van Rooijen ◽  
S. R. Weiss
Keyword(s):  
Type I Interferon ◽  
Type I ◽  
Cell Type ◽  
Cell Type Specific ◽  
Interferon Antagonism ◽  
Organ Tropism ◽  
Murine Coronavirus
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