Functional scintigraphy of the adrenal gland

Over the last 30 years nuclear medicine imaging of the adrenal gland and its lesions has been achieved by the exploitation of a number of physiological characteristics of this organ. By seeking and utilising features which are quantitatively or qualitatively different from those of the adjacent tissues, functional depiction of the adrenal gland and its diseases, which in most cases retain the basic physiology of their tissue of origin, including both the cortex and the medulla, are now a useful clinical reality. Agents widely used in clinical practice include: (a) uptake and storage of radiolabelled cholesterol analogues via the low density lipoprotein (LDL) receptor and cholesterol ester storage pool in the adrenal cortex ((131)I-6-beta-iodomethyl-norcholesterol, (75)Se-selenomethyl-norcholesterol); (b) catecholamine type I, presynaptic, uptake mechanism and intracellular granule uptake and storage mechanism in the adrenal medulla and extra-adrenal paraganglia ((131)I-, (123)I- and (124)I-meta-iodo-benzyl-guanidine (MIBG), (18)F-metafluoro-benzyl-guanidine); (c) cell surface receptor binding of peptides/neurotransmitters/modulators such as for the family of five subtypes of somatostatin receptors ((123)I-tyr-octreotide, (111)In-DTPA-octreotide, (111)In-DOTA-octreotide and many others); (d) although not specific for the adrenal gland, increased glycolysis by tumours, particularly the most malignant varieties, (18)F-2-fluoro-d-deoxyglucose can thus be expected to depict certain malignant lesions such as malignant pheochromocytomas (particularly the minority which are not detected by MIBG) and adrenal incidentalomas (particularly when they occur in patients with known extra-adrenal malignancies). There are a variety of adrenal tissue characteristics with potential for exploitation but which are not currently in clinical use, and which may, nevertheless, have potential as imaging agents. These include: (a) inhibitors of adrenal cortical steroid hormone synthesis enzymes (e.g. radiolabelled analogues of metyrapone); (b) radiolabelled lipoproteins which bind to adrenocortical LDL receptors; (c) inhibitors of catecholamine biosynthesis enzymes (e.g. radiolabelled analogues of tyrosine and related amino acids); (d) cell surface receptors for various peptides and hormones which may be over-expressed on adrenal cortical or adrenal medullary tumours (e.g. radiolabelled analogues of ACTH on adrenocortical cells of zona fasciculata or zona glomerulosa origin, neurotransmitter/hormone message peptides binding to cell surface receptors such as bombesin, vasoactive intestinal polypeptide, cholecystokinin and opiate peptides); (e) the adrenal cortex can also synthesise cholesterol ab initio from acetate, and preliminary studies with (11)C-acetate positron emission tomography have shown interesting results.

Download Full-text

Topological and Structural Plasticity of the Single Ig Fold and the Double Ig Fold Present in CD19

Biomolecules ◽

10.3390/biom11091290 ◽

2021 ◽

Vol 11 (9) ◽

pp. 1290 ◽

Cited By ~ 1

Author(s):

Philippe Youkharibache

Keyword(s):

Cell Surface ◽

3D Structure ◽

Cell Surface Receptor ◽

Cell Surface Receptors ◽

Structural Domain ◽

Surface Receptors ◽

Surface Receptor ◽

In Trans ◽

In Cis ◽

Ig Domain

The Ig fold has had a remarkable success in vertebrate evolution, with a presence in over 2% of human genes. The Ig fold is not just the elementary structural domain of antibodies and TCRs, it is also at the heart of a staggering 30% of immunologic cell surface receptors, making it a major orchestrator of cell–cell interactions. While BCRs, TCRs, and numerous Ig-based cell surface receptors form homo- or heterodimers on the same cell surface (in cis), many of them interface as ligand-receptors (checkpoints) on interacting cells (in trans) through their Ig domains. New Ig-Ig interfaces are still being discovered between Ig-based cell surface receptors, even in well-known families such as B7. What is largely ignored, however, is that the Ig fold itself is pseudosymmetric, a property that makes the Ig domain a versatile self-associative 3D structure and may, in part, explain its success in evolution, especially through its ability to bind in cis or in trans in the context of cell surface receptor–ligand interactions. In this paper, we review the Ig domains’ tertiary and quaternary pseudosymmetries, with particular attention to the newly identified double Ig fold in the solved CD19 molecular structure to highlight the underlying fundamental folding elements of Ig domains, i.e., Ig protodomains. This pseudosymmetric property of Ig domains gives us a decoding frame of reference to understand the fold, relate all Ig domain forms, single or double, and suggest new protein engineering avenues.

Download Full-text

Adenovirus Fiber Shaft Contains a Trimerization Element That Supports Peptide Fusion for Targeted Gene Delivery

Journal of Virology ◽

10.1128/jvi.01331-06 ◽

2006 ◽

Vol 80 (24) ◽

pp. 12324-12331 ◽

Cited By ~ 10

Author(s):

Jiali Li ◽

Sonya Lad ◽

Guang Yang ◽

Yunping Luo ◽

Milena Iacobelli-Martinez ◽

...

Keyword(s):

Gene Delivery ◽

Cell Surface ◽

Chimeric Protein ◽

Cell Surface Receptor ◽

Cell Surface Receptors ◽

Single Chain ◽

Single Chain Antibody ◽

Surface Receptors ◽

Fiber Assembly ◽

Fiber Protein

ABSTRACT Adenoviral (Ad) vectors have been widely used in human gene therapy clinical trials. However, their application has frequently been restricted by the unfavorable expression of cell surface receptors critical for Ad infection. Infections by Ad2 and Ad5 are largely regulated by the elongated fiber protein that mediates its attachment to a cell surface receptor, coxsackie and adenovirus receptor (CAR). The fiber protein is a homotrimer consisting of an N-terminal tail, a long shaft, and a C-terminal knob region that is responsible for high-affinity receptor binding and Ad tropism. Consequently, the modification of the knob region, including peptide insertion and C-terminal fusion of ligands for cell surface receptors, has become a major research focus for targeting gene delivery. Such manipulation tends to disrupt fiber assembly since the knob region contains a stabilization element for fiber trimerization. We report here the identification of a novel trimerization element in the Ad fiber shaft. We demonstrate that fiber fragments containing the N-terminal tail and shaft repeats formed stable trimers that assembled onto Ad virions independently of the knob region. This fiber shaft trimerization element (FSTE) exhibited a capacity to support peptide fusion. We showed that Ad, modified with a chimeric protein by direct fusion of the FSTE with a growth factor ligand or a single-chain antibody, delivered a reporter gene selectively. Together, these results indicate that the shaft region of Ad fiber protein contains a trimerization element that allows ligand fusion, which potentially broadens the basis for Ad vector development.

Download Full-text

Multiple Targets for Oxysterols in Their Regulation of the Immune System

Cells ◽

10.3390/cells10082078 ◽

2021 ◽

Vol 10 (8) ◽

pp. 2078

Author(s):

Lisa Reinmuth ◽

Cheng-Chih Hsiao ◽

Jörg Hamann ◽

Mette Rosenkilde ◽

John Mackrill

Keyword(s):

Immune System ◽

Cell Surface ◽

Oxidation Products ◽

Epigenetic Mechanism ◽

Cell Surface Receptor ◽

Cholesterol Oxidation ◽

Cell Surface Receptors ◽

Cholesterol Oxidation Products ◽

Surface Receptors ◽

Cellular Processes

Oxysterols, or cholesterol oxidation products, are naturally occurring lipids which regulate the physiology of cells, including those of the immune system. In contrast to effects that are mediated through nuclear receptors or by epigenetic mechanism, which take tens of minutes to occur, changes in the activities of cell-surface receptors caused by oxysterols can be extremely rapid, often taking place within subsecond timescales. Such cell-surface receptor effects of oxysterols allow for the regulation of fast cellular processes, such as motility, secretion and endocytosis. These cellular processes play critical roles in both the innate and adaptive immune systems. This review will survey the two broad classes of cell-surface receptors for oxysterols (G-protein coupled receptors (GPCRs) and ion channels), the mechanisms by which cholesterol oxidation products act on them, and their presence and functions in the different cell types of the immune system. Overall, this review will highlight the potential of oxysterols, synthetic derivatives and their receptors for physiological and therapeutic modulation of the immune system.

Download Full-text

Dynamics of signal transduction after aggregation of cell-surface receptors: studies on the type I receptor for IgE.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.91.8.3087 ◽

1994 ◽

Vol 91 (8) ◽

pp. 3087-3091 ◽

Cited By ~ 31

Author(s):

U. M. Kent ◽

S. Y. Mao ◽

C. Wofsy ◽

B. Goldstein ◽

S. Ross ◽

...

Keyword(s):

Signal Transduction ◽

Cell Surface ◽

Cell Surface Receptors ◽

Type I ◽

Surface Receptors

Download Full-text

Recognition of human urine α-N-acetylglucosaminidase by rat hepatocytes. Involvement of receptors specific for galactose, mannose 6-phosphate and mannose

Biochemical Journal ◽

10.1042/bj1800413 ◽

1979 ◽

Vol 180 (2) ◽

pp. 413-419 ◽

Cited By ~ 28

Author(s):

K Ullrich ◽

R Basner ◽

V Gieselmann ◽

K Von Figura

Keyword(s):

Cell Surface ◽

Human Urine ◽

Rat Hepatocytes ◽

Cell Surface Receptor ◽

Cell Surface Receptors ◽

Minor Role ◽

Isolated Rat Hepatocytes ◽

Surface Receptors ◽

Terminal Galactose ◽

Mannose 6 Phosphate

Adsorptive endocytosis of alpha-N-acetylglucosaminidase from human urine by isolated rat hepatocytes is inhibited by glycoproteins, polysaccharides and sugars that are known to bind to cell-surface receptors specific for either terminal galactose/N-acetylgalactosamine residues, terminal mannose residues or mannose 6-phosphate residues. Recognition of alpha-N-acetylglucosaminidase by a cell-surface receptor specific for terminal galactose/N-acetylgalactosamine residues is supported by the observations (a) that neuraminidase pretreatment of the enzyme enhances endocytosis, (b) that beta-galactosidase treatment decreases endocytosis and (c) that neuraminidase pretreatment of hepatocytes decreases alpha-N-acetylglucosaminidase endocytosis. Recognition of alpha-N-acetylglucosaminidase via receptors recognizing mannose 6-phosphate residues is lost after treatment of the enzyme with alkaline phosphatase and endoglucosaminidase H. The effect of endoglucosaminidase H supports the view that the mannose 6-phosphate residues reside in N-glycosidically linked oligosaccharide side chains of the high-mannose type. The weak inhibition of endocytosis produced by compounds known to interact with cell-surface receptors specific for mannose residues suggests that this recognition system plays only a minor role in the endocytosis of lysosomal alpha-N-acetylglucosaminidase by hepatocytes.

Download Full-text

SPaRTAN, a computational framework for linking cell-surface receptors to transcriptional regulators

Nucleic Acids Research ◽

10.1093/nar/gkab745 ◽

2021 ◽

Vol 49 (17) ◽

pp. 9633-9647

Author(s):

Xiaojun Ma ◽

Ashwin Somasundaram ◽

Zengbiao Qi ◽

Douglas J Hartman ◽

Harinder Singh ◽

...

Keyword(s):

Cell Surface ◽

Single Cell ◽

Transcriptional Regulators ◽

Cell Types ◽

Receptor Expression ◽

Cell Surface Receptor ◽

Cell Surface Receptors ◽

Surface Receptors ◽

Surface Receptor ◽

Context Specific

Abstract The identity and functions of specialized cell types are dependent on the complex interplay between signaling and transcriptional networks. Recently single-cell technologies have been developed that enable simultaneous quantitative analysis of cell-surface receptor expression with transcriptional states. To date, these datasets have not been used to systematically develop cell-context-specific maps of the interface between signaling and transcriptional regulators orchestrating cellular identity and function. We present SPaRTAN (Single-cell Proteomic and RNA based Transcription factor Activity Network), a computational method to link cell-surface receptors to transcription factors (TFs) by exploiting cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) datasets with cis-regulatory information. SPaRTAN is applied to immune cell types in the blood to predict the coupling of signaling receptors with cell context-specific TFs. Selected predictions are validated by prior knowledge and flow cytometry analyses. SPaRTAN is then used to predict the signaling coupled TF states of tumor infiltrating CD8+ T cells in malignant peritoneal and pleural mesotheliomas. SPaRTAN enhances the utility of CITE-seq datasets to uncover TF and cell-surface receptor relationships in diverse cellular states.

Download Full-text

Expression of a type I insulin-like growth factor receptor with low affinity for insulin-like growth factor II

Biochemical Journal ◽

10.1042/bj2810413 ◽

1992 ◽

Vol 281 (2) ◽

pp. 413-417 ◽

Cited By ~ 41

Author(s):

E L Germain-Lee ◽

M Janicot ◽

R Lammers ◽

A Ullrich ◽

S J Casella

Keyword(s):

Growth Factor ◽

Cell Surface ◽

Growth Factor Receptor ◽

Cell Surface Receptors ◽

Type I ◽

Insulin Like Growth Factor ◽

Surface Receptors ◽

3T3 Fibroblasts ◽

Igf I ◽

Nih 3T3

We investigated the binding properties of the type I insulin-like growth factor (IGF) receptor expressed in NIH-3T3 fibroblasts transfected with a human type I receptor cDNA. Cell surface receptors bound IGF-I with KD = 1 nM as predicted. Although recent studies have suggested that IGF-I and IGF-II bind to type I receptors with near-equal affinity, the receptors in this system bound IGF-II with much lower affinity (KD = 15-20 nM). When type I receptors from the transfected cells were solubilized and immunopurified, however, both 125I-IGF-I and 125I-IGF-II bound to the purified receptors with extremely high and relatively similar affinities (KD = 8 and 17 pM respectively). Thus the immunopurified receptors had higher affinity but lower specificity for the two ligands. The monoclonal antibody alpha IR-3 effectively inhibited IGF-I binding to cell surface receptors (75 +/- 10%), but did not inhibit IGF-II binding. In the purified receptor assay, alpha IR-3 also inhibited IGF-I binding more effectively than IGF-II binding (38 +/- 7% versus 10 +/- 4%). We conclude that the products of this cDNA can account for the binding patterns that we previously observed in receptors immunopurified from human placenta. The differential effect of alpha IR-3 on IGF-I versus IGF-II raises the possibility that these homologous growth factors bind to immunologically distinct epitopes on the type I receptor.

Download Full-text

Topological and Structural Plasticity of the single Ig fold and the double Ig fold present in CD19

10.1101/2021.06.04.447059 ◽

2021 ◽

Author(s):

Philippe Youkharibache

Keyword(s):

Cell Surface ◽

3D Structure ◽

Cell Surface Receptor ◽

Cell Surface Receptors ◽

Structural Domain ◽

Surface Receptors ◽

Surface Receptor ◽

In Trans ◽

In Cis ◽

Ig Domain

The Ig-fold has had a remarkable success in vertebrate evolution, with a presence in over 2% of human genes. The Ig-fold is not just the elementary structural domain of antibodies and TCRs, it is also at the heart of a staggering 30% of immunologic cell surface receptors, making it a major orchestrator of cell-cell-interactions. While BCRs, TCRs, and numerous Ig-based cell surface receptors form homo or heterodimers on the same cell surface (in cis), many of them interface as ligand-receptors (checkpoints) on interacting cells (in trans) through their Ig domains. New Ig-Ig interfaces are still being discovered between Ig-based cell surface receptors, even in well known families such as B7. What is largely ignored however is that the Ig-fold itself is pseudo-symmetric, a property that makes the Ig-domain a versatile self-associative 3D structure and may in part explain its success in evolution, especially through its ability to bind in cis or in trans in the context of cell surface receptor-ligand interactions. In this paper we review the Ig domains tertiary and quaternary pseudo symmetries, with a particular attention to the newly identified double Ig fold in the solved CD19 molecular structure to highlight the underlying fundamental folding elements of Ig domains, i.e. Ig protodomains. This pseudosymmetric property of Ig domains gives us a decoding frame of reference to understand the fold, relate all Ig-domain forms, single or double, and suggest new protein engineering avenues.

Download Full-text