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Dopamine Receptors, Signaling Pathways, and Drugs
Published in Nira Ben-Jonathan, Dopamine, 2020
Several paradigms have been proposed to address the mechanism of multimer formation [34,35]. One model stipulates that homodimers are preassembled intracellularly before they reach the cell membrane. A second model assumes that heterodimers are generated by a free-floating, “collision-coupling” type of interaction within the cell membrane. A third model implicates a more regulated heterodimer formation through an association with chaperones that partition the receptor partners into membrane microdomains such as lipid rafts or caveolae.
Mechanism of Action of Bexarotene
Published in Ayse Serap Karadag, Berna Aksoy, Lawrence Charles Parish, Retinoids in Dermatology, 2019
Catherine M. Ludwig, Claire Wilson, Brandon Roman, Maria M. Tsoukas
Gene regulation by RXRs has significant effects in controlling cellular growth, proliferation, differentiation, and apoptosis. When bexarotene is administered with an RAR agonist, it leads to upregulation of transglutaminase I, an enzyme actively involved in the apoptotic cascade (10). RXRs can form both homodimers and heterodimers. Within heterodimers, RXR can serve as either an active or silent partner to its ligand. The active partner form of RXR will allow activation of the ligand receptor by RA leading to its gene transcription capabilities. As a silent partner, the heterodimer of RXR prevents its ligand from responding to RA (11). Through its on/off effects on the metabolism of fatty acids, cholesterol, amino acids, and carbohydrates, RXR has been said to be a “master regulator” of the metabolic effects of retinoids (11).
Instability of Human Mitochondrial DNA, Nuclear Genes and Diseases
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
The last subgroup of mitochondrial diseases with nucleotide pool perturbations is the one resulting from defective transport between mitochondria and the cytosol. Here two main defects can be described – mutations in SLC25A4 (formerly called ANT1) and MPV 17. SLC25A4 (4q35.1) encoding adenosine nucleotides translocator, an inner mitochondrial membrane protein responsible for the transport of ATP, produced in the process of oxidative respiration, from mitochondrial matrix to intermembrane space and ADP, necessary as a substrate for ATP production, from intermembrane space to mitochondrial matrix. Mutations in SLC25A4 were in fact the first described defect of mtDNA maintenance presenting as autosomal dominant PEO43. The dominance of SLC25A4 mutations can be easily explained by the structure of the adenine nucleotide translocator. The protein forms a homodimer. When proteins produced from one of the alleles are defective it can be predicted that up to 3/4 of translocators can have improper structure and function. Recently the third player in this group has appeared: AGK (7q34) gene encoding acylglicerol synthase. It is necessary for membrane lipids synthesis and therefore influences mitochondrial membrane composition. It seems that mutations in AGK lead to improper ANT1 assembly, as the nucleotide translocator is bound to the inner membrane phosphatidic acid and cardiolipin44.
F11R/JAM-A: why do platelets express a molecule which is also present in tight junctions?
Published in Platelets, 2023
Piotr Kamola, Anna Babinska, Tomasz Przygodzki
As mentioned above, F11R/JAM-A molecules are capable of forming homodimers. This homodimerization occurs in cis-configuration when the dimer is formed by the molecules located in the same cell (Figure 2b). The molecules can also interact in the trans-configuration when they are located on the membrane of two adjacent cells20 (Figure 2c). It is not clear whether cis-homodimerization is required for trans-homophilic interactions. Some data suggest that monomeric F11R/JAM-A can also interact with its counterpart on an adjacent cell.20 The sites responsible for cis- and trans-homophilic interactions lay in distinct parts of D1 domain of the molecule.20 Both types of interactions are believed to be associated with the function of the protein which will be described further.
DMSO-tolerant ornithine decarboxylase (ODC) tandem assay optimised for high-throughput screening
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Mingu Gordon Park, Suyeon Yellena Kim, C. Justin Lee
To overcome this problem, we used Strep-tag system, which is known to be compatible with any expression system including mammalian cells41. We performed overexpression of Twin-Strep-tagged human ODC in Expi293FTM cells followed by a two-step protein purification (Figure 2B). Firstly, the Twin-Strep-tagged human ODC was purified from cell lysate via Strep-Tactin affinity chromatography. The elution of Twin-Strep-tagged human ODC was carried out with elution buffer containing 10 mM biotin. The eluted recombinant human ODC exhibited a size of 51 kDa on SDS-PAGE gel under reducing conditions (Figure 2C). Secondly, we further purified the eluted fractions by size-exclusion chromatography (Figure 2D), because ODC is catalytically active only in a homodimeric form23,32,42. Considering the molecular weight of human ODC homodimer (102 kDa), we confirmed that sample peak fractions (14th to 20th fractions) between standard peak B (158 kDa) and C (44 kDa) contained biologically active human ODC homodimers (Figure 2E, top and middle panels) by performing the ODC tandem assay (Figure 2E, bottom panel), Coomassie Blue staining and western blot analysis (Figure 2D). These results indicate that we successfully obtained biologically active human ODC homodimers for HTS.
In vitro study of the effects of DC electric fields on cell activities and gene expression in human choriocarcinoma cells
Published in Electromagnetic Biology and Medicine, 2021
Jinxin Chen, Linbo Guan, Ping Fan, Xinghui Liu, Rui Liu, Yu Liu, Huai Bai
ErbB belongs to the human epidermal growth factor receptor (HER) family of transmembrane tyrosine kinases, including ErbB1(EGFR), ErbB2, ErbB3, and ErbB4 (Sirica 2008). Upon ligand binding, ErbB homodimers or heterodimers are activated by autophosphorylation and then combine with some intermediate proteins, which elicit several downstream cascades and lead to important biological effects, including cell movement, proliferation, adhesion, and differentiation (Linggi and Carpenter 2006; Sirica 2008). Our results showed that the expression of EGFR, ErbB4, Crk (CrkL), CDKN1A (P21), and JUN genes was upregulated in the ErbB signaling pathway in choriocarcinoma cells stimulated by DC EF. Several studies have shown that the overexpression or overactivity of EGFR is associated with enhanced migration or proliferation of several types of cells, including keratinocytes and myofibroblasts (Andl et al. 2003; Zuo et al. 2018).