scholarly journals Transport, functions, and interaction of calcium and manganese in plant organellar compartments

2021 ◽  
Author(s):  
Jie He ◽  
Nico Rössner ◽  
Minh T T Hoang ◽  
Santiago Alejandro ◽  
Edgar Peiter
Keyword(s):  
Molecular Mechanisms ◽  
Metal Tolerance ◽  
Essential Elements ◽  
Natural Resistance ◽  
Ionic Radii ◽  
Bivalent Cation ◽  
Cyclic Nucleotide Gated Channels ◽  
Complex Processes ◽  
Open Questions ◽  
Golgi Network

Abstract Calcium (Ca2+) and manganese (Mn2+) are essential elements for plants and have similar ionic radii and binding coordination. They are assigned specific functions within organelles, but share many transport mechanisms to cross organellar membranes. Despite their points of interaction, those elements are usually investigated and reviewed separately. This review takes them out of this isolation. It highlights our current mechanistic understanding and points to open questions of their functions, their transport, and their interplay in the endoplasmic reticulum (ER), vesicular compartments [Golgi apparatus, trans-Golgi Network (TGN), prevacuolar compartment (PVC)], vacuoles, chloroplasts, mitochondria, and peroxisomes. Complex processes demanding these cations, such as Mn2+-dependent glycosylation or systemic Ca2+ signaling, are covered in some detail if they have not been reviewed recently or if recent findings add to current models. The function of Ca2+ as signaling agent released from organelles into the cytosol and within the organelles themselves is a recurrent theme of this review, again keeping the interference by Mn2+ in mind. The involvement of organellar channels [e.g., Glutamate-Receptor-Likes (GLRs), Cyclic-Nucleotide-Gated Channels (CNGCs), Mitochondrial Conductivity Units (MCUs), Two-Pore Channel1 (TPC1)], transporters [e.g., Natural-Resistance-Associated Macrophage Proteins (NRAMPs), Calcium Exchangers (CAXs), Metal-Tolerance Proteins (MTPs), Bivalent-Cation Transporters (BICATs)] and pumps [Autoinhibited Ca2+-ATPases (ACAs), ER Ca2+-ATPases (ECAs)] in the import and export of organellar Ca2+ and Mn2+ is scrutinized, whereby current controversial issues are pointed out. Mechanisms in animals and yeast are taken into account where they may provide a blueprint for processes in plants, in particular with respect to tunable molecular mechanisms of Ca2+-versus-Mn2+ selectivity.

scholarly journals Anaphylactic Degranulation of Mast Cells: Focus on Compound Exocytosis

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Ofir Klein ◽  
Ronit Sagi-Eisenberg
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Molecular Mechanisms ◽  
Secretory Granules ◽  
Cell Types ◽  
Secretory Cells ◽  
Regulated Exocytosis ◽  
Open Questions ◽  
Conflicting Evidence ◽  
Compound Exocytosis

Anaphylaxis is a notorious type 2 immune response which may result in a systemic response and lead to death. A precondition for the unfolding of the anaphylactic shock is the secretion of inflammatory mediators from mast cells in response to an allergen, mostly through activation of the cells via the IgE-dependent pathway. While mast cells are specialized secretory cells that can secrete through a variety of exocytic modes, the most predominant mode exerted by the mast cell during anaphylaxis is compound exocytosis—a specialized form of regulated exocytosis where secretory granules fuse to one another. Here, we review the modes of regulated exocytosis in the mast cell and focus on compound exocytosis. We review historical landmarks in the research of compound exocytosis in mast cells and the methods available for investigating compound exocytosis. We also review the molecular mechanisms reported to underlie compound exocytosis in mast cells and expand further with reviewing key findings from other cell types. Finally, we discuss the possible reasons for the mast cell to utilize compound exocytosis during anaphylaxis, the conflicting evidence in different mast cell models, and the open questions in the field which remain to be answered.

scholarly journals Hepatic stellate cells: current state and open questions

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Claus Kordes ◽  
Hans H. Bock ◽  
Doreen Reichert ◽  
Petra May ◽  
Dieter Häussinger
Keyword(s):  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Essential Elements ◽  
Future Research ◽  
Heinrich Heine ◽  
Current State ◽  
Open Questions ◽  
Sinusoidal Endothelium ◽  
Cell Niche ◽  
Space Of Disse

Abstract This review article summarizes 20 years of our research on hepatic stellate cells within the framework of two collaborative research centers CRC575 and CRC974 at the Heinrich Heine University. Over this period, stellate cells were identified for the first time as mesenchymal stem cells of the liver, and important functions of these cells in the context of liver regeneration were discovered. Furthermore, it was determined that the space of Disse – bounded by the sinusoidal endothelium and hepatocytes – functions as a stem cell niche for stellate cells. Essential elements of this niche that control the maintenance of hepatic stellate cells have been identified alongside their impairment with age. This article aims to highlight previous studies on stellate cells and critically examine and identify open questions and future research directions.

scholarly journals Eradication of HIV by Transplantation of CCR5-Deficient Hematopoietic Stem Cells

2011 ◽  
Vol 11 ◽  
pp. 1068-1076 ◽  
Author(s):  
Gero Hütter ◽  
Susanne Ganepola
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Treatment Strategies ◽  
Allogeneic Transplantation ◽  
Lymphoid Cells ◽  
Natural Resistance ◽  
Tissue Samples ◽  
Hematopoietic Stem ◽  
Open Questions ◽  
Clinical Consequences

Today, 30 years after the onset of the HIV pandemic, although treatment strategies have considerably improved, there is still no cure for the disease. Recently, we described a successful hematopoietic stem cell transplantation in an HIV-1–infected patient, transferring donor-derived cells with a natural resistance against HIV infection. These hematopoietic stem cells engrafted, proliferated, and differentiated into mature myeloid and lymphoid cells. To date, the patient has not required any antiretroviral treatment, more than 4 years after allogeneic transplantation. In the analysis of peripheral blood cells and different tissue samples, including gut, liver, and brain, no viral load or proviral DNA could be detected. Our report raises the hope for further targeted treatment strategies against HIV and represents a successful personalized treatment with allogeneic stem cells carrying a beneficial gene. However, this case has ignited a controversy regarding the question of whether this patient has achieved complete eradication of HIV or not. Here we give an update on open questions, unsolved aspects, and clinical consequences concerning this unique case.

scholarly journals Transmembrane-truncated αvβ3 integrin retains high affinity for ligand binding: evidence for an ‘inside-out’ suppressor?

1998 ◽  
Vol 330 (2) ◽  
pp. 861-869 ◽  
Author(s):  
J. Raj MEHTA ◽  
Beate DIEFENBACH ◽  
Alex BROWN ◽  
Eilish CULLEN ◽  
Alfred JONCZYK ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Wound Repair ◽  
Molecular Mechanisms ◽  
Full Length ◽  
Αvβ3 Integrin ◽  
Cytoplasmic Domains ◽  
Bivalent Cation ◽  
High Affinity ◽  
Cellular Environment

The molecular mechanisms of αvβ3 integrin affinity regulation have important biological implications in tumour development, wound repair and angiogenesis. We expressed, purified and characterized recombinant forms of human αvβ3 (r-αvβ3) and compared the activation state of these with αvβ3 in its cellular environment. The ligand specificity and selectivity of recombinant full-length and double transmembrane truncations of r-αvβ3 cloned in BacPAK6 vectors and expressed in Sf9 and High Five insect cells were compared with those of native placental αvβ3 and the receptor in situ on the cell surface. r-αvβ3 integrins were purified by affinity chromatography from detergent extracts of cells (full-length), and from the culture medium of cells expressing double-truncated r-αvβ3. r-αvβ3 had the same epitopes, ligand-binding specificities, bivalent cation requirements and susceptibility to RGD-containing peptides as native αvβ3. On M21-L4 melanoma cells, αvβ3 mediated binding to vitronectin, but not to fibrinogen unless activated with Mn2+. Non-activated αIIbβ3 integrin as control in M21-L-IIb cells had the opposite profile, mediating binding to fibrinogen, but not to vitronectin unless activated with Mn2+. Thus these receptors had moderate to low ligand affinity. In marked contrast, purified αvβ3 receptors, with or without transmembrane and cytoplasmic domains, were constitutively of high affinity and able to bind strongly to vitronectin, fibronectin and fibrinogen under physiological conditions. Our data suggest that, in contrast with the positive regulation of αIIbβ3 in situ, intracellular controls lower the affinity of αvβ3, and the cytoplasmic domains may act as a target for negative regulators of αvβ3 activity.

Keratin function and regulation in tissue homeostasis and pathogenesis

2012 ◽  
Vol 3 (2) ◽  
pp. 161-173 ◽  
Author(s):  
Wera Roth ◽  
Mechthild Hatzfeld ◽  
Maik Friedrich ◽  
Sören Thiering ◽  
Thomas M. Magin
Keyword(s):  
Posttranslational Modifications ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Growth Control ◽  
Specific Expression ◽  
Intermediate Filament Proteins ◽  
Mesenchymal Transition ◽  
Keratin Expression ◽  
Open Questions ◽  
Formidable Challenge

AbstractEpithelial tissues act as hubs in metabolism and communication and protect the organism against dehydration, infections, pharmacological and physical stress. Keratin intermediate filament proteins are well established as major cytoskeletal players in maintaining epithelial integrity. More recently, an involvement of keratins in growth control and organelle functions has emerged. Disruption of the keratin cytoskeleton by mutations or its reorganization following posttranslational modifications can render epithelia susceptible to tissue damage and various stresses, while loss of keratin expression is a hallmark of epithelial-mesenchymal transition (EMT). To understand the molecular mechanisms by which keratins perform their functions remains a formidable challenge. Based on selected examples, we will discuss how cell-specific expression of keratin isotypes affects cytoarchitecture and cell behavior. Further, we ask how posttranslational modifications alter keratin organization and interactions during signaling. Next, we discuss pathomechanisms of epidermal keratin disorders in the light of novel data. Finally, we raise open questions and point out future directives.

Retrograde trafficking of both Golgi complex and TGN markers to the ER induced by nordihydroguaiaretic acid and cyclofenil diphenol

1998 ◽  
Vol 111 (7) ◽  
pp. 951-965 ◽  
Author(s):  
D. Drecktrah ◽  
P. de Figueiredo ◽  
R.M. Mason ◽  
W.J. Brown
Keyword(s):  
Golgi Complex ◽  
Membrane Trafficking ◽  
Molecular Mechanisms ◽  
Nordihydroguaiaretic Acid ◽  
Retrograde Transport ◽  
Lipoxygenase Inhibitor ◽  
Golgi Stack ◽  
Golgi Network ◽  
In Vivo Effects

Previous studies have shown that the Golgi stack and the trans-Golgi network (TGN) may play a role in capturing escaped resident endoplasmic reticulum (ER) proteins, and directing their retrograde transport back to that organelle. Whether this retrograde movement represents a highly specific or more generalized membrane trafficking pathway is unclear. To better understand both the retrograde and anterograde trafficking pathways of the secretory apparatus, we examined more closely the in vivo effects of two structurally unrelated compounds, the potent lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA), and the non-steroidal estrogen cyclofenil diphenol (CFD), both of which are known to inhibit secretion. In the presence of these compounds, transport of vesicular stomatitis virus G membrane glycoprotein from the ER to the Golgi complex, and from the TGN to the cell surface, was inhibited potently and rapidly. Surprisingly, we found that NDGA and CFD stimulated the rapid, but not concomitant, retrograde movement of both Golgi stack and TGN membrane proteins back to the ER until both organelles were morphologically absent from cells. Both NDGA- and CFD-stimulated TGN and Golgi retrograde membrane trafficking were inhibited by microtubule depolymerizing agents and energy poisons. Removal of NDGA and CFD resulted in the complete, but not concomitant, reformation of both Golgi stacks and their closely associated TGN compartments. These studies suggest that NDGA and CFD unmask a generalized bulk recycling pathway to the ER for both Golgi and TGN membranes and, further, that NDGA and CFD are useful for investigating the molecular mechanisms that control the formation and maintenance of both the Golgi stack proper and the TGN.

Molecular Mechanisms of Heavy Metal Tolerance in Plants

2020 ◽  
pp. 125-136
Author(s):  
Nasser Delangiz ◽  
Bahman Khoshru ◽  
Behnam Asgari Lajayer ◽  
Mansour Ghorbanpour ◽  
Solmaz Kazemalilou
Keyword(s):  
Heavy Metal ◽  
Molecular Mechanisms ◽  
Metal Tolerance ◽  
Heavy Metal Tolerance

scholarly journals HID-1 is required for homotypic fusion of immature secretory granules during maturation

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Wen Du ◽  
Maoge Zhou ◽  
Wei Zhao ◽  
Dongwan Cheng ◽  
Lifen Wang ◽  
...  
Keyword(s):  
Secretory Granule ◽  
Molecular Mechanisms ◽  
Secretory Granules ◽  
Three Dimensional ◽  
Conditional Knockout ◽  
Active Peptides ◽  
Early Maturation ◽  
Proinsulin Processing ◽  
Granule Maturation ◽  
Golgi Network

Secretory granules, also known as dense core vesicles, are generated at the trans-Golgi network and undergo several maturation steps, including homotypic fusion of immature secretory granules (ISGs) and processing of prehormones to yield active peptides. The molecular mechanisms governing secretory granule maturation are largely unknown. Here, we investigate a highly conserved protein named HID-1 in a mouse model. A conditional knockout of HID-1 in pancreatic β cells leads to glucose intolerance and a remarkable increase in the serum proinsulin/insulin ratio caused by defective proinsulin processing. Large volume three-dimensional electron microscopy and immunofluorescence imaging reveal that ISGs are much more abundant in the absence of HID-1. We further demonstrate that HID-1 deficiency prevented secretory granule maturation by blocking homotypic fusion of immature secretory granules. Our data identify a novel player during the early maturation of immature secretory granules.

scholarly journals Sarcopenia – Molecular mechanisms and open questions

2021 ◽  
Vol 65 ◽  
pp. 101200
Author(s):  
Petra Wiedmer ◽  
Tobias Jung ◽  
José Pedro Castro ◽  
Laura C.D. Pomatto ◽  
Patrick Y. Sun ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Open Questions

scholarly journals Cellular functions and molecular mechanisms of non-lysine ubiquitination

Open Biology ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 190147 ◽  
Author(s):  
Amie J. McClellan ◽  
Sophie Heiden Laugesen ◽  
Lars Ellgaard
Keyword(s):  
Dna Repair ◽  
Molecular Mechanisms ◽  
Future Perspectives ◽  
Cellular Functions ◽  
The Past ◽  
Protein Ubiquitination ◽  
Open Questions ◽  
Lysine Residues ◽  
Molecular Machinery ◽  
Mechanistic Basis

Protein ubiquitination is of great cellular importance through its central role in processes such as degradation, DNA repair, endocytosis and inflammation. Canonical ubiquitination takes place on lysine residues, but in the past 15 years non-lysine ubiquitination on serine, threonine and cysteine has been firmly established. With the emerging importance of non-lysine ubiquitination, it is crucial to identify the responsible molecular machinery and understand the mechanistic basis for non-lysine ubiquitination. Here, we first provide an overview of the literature that has documented non-lysine ubiquitination. Informed by these examples, we then discuss the molecular mechanisms and cellular implications of non-lysine ubiquitination, and conclude by outlining open questions and future perspectives in the field.

Sign in / Sign up

Export Citation Format

Share Document