scholarly journals ASC-1, PAT2, and P2RX5 are cell surface markers for white, beige, and brown adipocytes

2014 ◽  
Vol 6 (247) ◽  
pp. 247ra103-247ra103 ◽  
Author(s):  
Siegfried Ussar ◽  
Kevin Y. Lee ◽  
Simon N. Dankel ◽  
Jeremie Boucher ◽  
Max-Felix Haering ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cell Surface ◽  
Cell Types ◽  
Amino Acid Transporter ◽  
Specific Cell ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
Brown Adipocytes ◽  
Beige Adipocytes ◽  
Acid Transporter

White, beige, and brown adipocytes are developmentally and functionally distinct but often occur mixed together within individual depots. To target white, beige, and brown adipocytes for diagnostic or therapeutic purposes, a better understanding of the cell surface properties of these cell types is essential. Using a combination of in silico, in vitro, and in vivo methods, we have identified three new cell surface markers of adipose cell types. The amino acid transporter ASC-1 is a white adipocyte–specific cell surface protein, with little or no expression in brown adipocytes, whereas the amino acid transporter PAT2 and the purinergic receptor P2RX5 are cell surface markers expressed in classical brown and beige adipocytes in mice. These markers also selectively mark brown/beige and white adipocytes in human tissue. Thus, ASC-1, PAT2, and P2RX5 are membrane surface proteins that may serve as tools to identify and target white and brown/beige adipocytes for therapeutic purposes.

Towards an indirect screening technique facilitating detection of cellular populations bearing specific cell surface markers

2010 ◽  
Vol 26 (6) ◽  
pp. 1544-1550
Author(s):  
Sandeep K. Arora ◽  
Rohit Sharma ◽  
Gagandeep Kaur ◽  
Preeti Bhoria ◽  
Maryada Sharma ◽  
...  
Keyword(s):  
Cell Surface ◽  
Specific Cell ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
Screening Technique ◽  
Specific Cell Surface

Galectin-lattice sustains function of cationic amino acid transporter and insulin secretion of pancreatic β cells

2020 ◽  
Vol 167 (6) ◽  
pp. 587-596 ◽  
Author(s):  
Kento Maeda ◽  
Masayoshi Tasaki ◽  
Yukio Ando ◽  
Kazuaki Ohtsubo
Keyword(s):  
Insulin Secretion ◽  
Amino Acid ◽  
Cell Surface ◽  
Amino Acid Transporter ◽  
Cell Surface Expression ◽  
Cationic Amino Acid Transporter ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Cationic Amino Acid ◽  
Acid Transporter

Abstract Maintenance of cell surface residency and function of glycoproteins by lectins are essential for regulating cellular functions. Galectins are β-galactoside-binding lectins and form a galectin-lattice, which regulates stability, clustering, membrane sub-domain localization and endocytosis of plasmalemmal glycoproteins. We have previously reported that galectin-2 (Gal-2) forms a complex with cationic amino acid transporter 3 (CAT3) in pancreatic β cells, although the biological significance of the molecular interaction between Gal-2 and CAT3 has not been elucidated. In this study, we demonstrated that the structure of N-glycan of CAT3 was either tetra- or tri-antennary branch structure carrying β-galactosides, which works as galectin-ligands. Indeed, CAT3 bound to Gal-2 using β-galactoside epitope. Moreover, the disruption of the glycan-mediated bindings between galectins and CAT3 significantly reduced cell surface expression levels of CAT3. The reduced cell surface residency of CAT3 attenuated the cellular arginine uptake activities and subsequently reduced nitric oxide production, and thus impaired the arginine-stimulated insulin secretion of pancreatic β cells. These results indicate that galectin-lattice stabilizes CAT3 by preventing endocytosis to sustain the arginine-stimulated insulin secretion of pancreatic β cells. This provides a novel cell biological insight into the endocrinological mechanism of nutrition metabolism and homeostasis.

Regulatory pathways and uptake ofl-DOPA by capillary cerebral endothelial cells, astrocytes, and neuronal cells

2001 ◽  
Vol 280 (2) ◽  
pp. C333-C342 ◽  
Author(s):  
B. Sampaio-Maia ◽  
M. P. Serrão ◽  
P. Soares-da-Silva
Keyword(s):  
Amino Acid ◽  
Neuroblastoma Cells ◽  
Cell Types ◽  
Amino Acid Transporter ◽  
Nitric Oxide Donor ◽  
Intracellular Camp ◽  
Regulatory Pathways ◽  
Dopa Accumulation ◽  
Acid Transporter ◽  
Dopa Uptake

We examined the nature and regulation of the inwardl-3,4-dihydroxyphenylalanine (l-DOPA) transporter in rat capillary cerebral endothelial (RBE4) cells, type 1 astrocytes (DI TNC1), and Neuro-2a neuroblastoma cells. In all three cell types, the inward transfer of l-DOPA was largely promoted through the 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid-sensitive and sodium-independent L-type amino acid transporter. Only in DI TNC1 cells was the effect of maneuvers that increase intracellular cAMP levels accompanied by increases inl-DOPA uptake. Also, only in DI TNC1 cells was the effect of the guanylyl cyclase inhibitor LY-83583 accompanied by a 65% increase in l-DOPA accumulation, whereas the nitric oxide donor sodium nitroprusside produced a 25% decrease inl-DOPA accumulation. In all three cell types, the Ca2+/calmodulin inhibitors calmidazolium and trifluoperazine inhibited l-DOPA uptake in a noncompetitive manner. Thapsigargin (1 and 3 μM) and A-23187 (1 and 3 μM) failed to alter l-DOPA accumulation in RBE4 and Neuro-2a cells but markedly increased l-DOPA uptake in DI TNC1cells. We concluded that l-DOPA in RBE4, DI TNC1, and Neuro-2a cells is transported through the L-type amino acid transporter and appears to be under the control of Ca2+/calmodulin-mediated pathways. Astrocytes, however, are endowed with other processes that appear to regulate the accumulation of l-DOPA, responding positively to increases in intracellular Ca2+ and cAMP and to decreases in cGMP.

scholarly journals The L-type amino acid transporter LAT1 inhibits osteoclastogenesis and maintains bone homeostasis through the mTORC1 pathway

2019 ◽  
Vol 12 (589) ◽  
pp. eaaw3921
Author(s):  
Kakeru Ozaki ◽  
Takanori Yamada ◽  
Tetsuhiro Horie ◽  
Atsushi Ishizaki ◽  
Manami Hiraiwa ◽  
...  
Keyword(s):  
Amino Acid ◽  
Bone Loss ◽  
Glycogen Synthase ◽  
Amino Acid Transporter ◽  
Nuclear Accumulation ◽  
Specific Cell ◽  
Nuclear Factor ◽  
Bone Homeostasis ◽  
Mtorc1 Pathway ◽  
Acid Transporter

L-type amino acid transporter 1 (LAT1), which is encoded by solute carrier transporter 7a5 (Slc7a5), plays a crucial role in amino acid sensing and signaling in specific cell types, contributing to the pathogenesis of cancer and neurological disorders. Amino acid substrates of LAT1 have a beneficial effect on bone health directly and indirectly, suggesting a potential role for LAT1 in bone homeostasis. Here, we identified LAT1 in osteoclasts as important for bone homeostasis. Slc7a5 expression was substantially reduced in osteoclasts in a mouse model of ovariectomy-induced osteoporosis. The osteoclast-specific deletion of Slc7a5 in mice led to osteoclast activation and bone loss in vivo, and Slc7a5 deficiency increased osteoclastogenesis in vitro. Loss of Slc7a5 impaired activation of the mechanistic target of rapamycin complex 1 (mTORC1) pathway in osteoclasts, whereas genetic activation of mTORC1 corrected the enhanced osteoclastogenesis and bone loss in Slc7a5-deficient mice. Last, Slc7a5 deficiency increased the expression of nuclear factor of activated T cells, cytoplasmic 1 (Nfatc1) and the nuclear accumulation of NFATc1, a master regulator of osteoclast function, possibly through the canonical nuclear factor κB pathway and the Akt–glycogen synthase kinase 3β signaling axis, respectively. These findings suggest that the LAT1-mTORC1 axis plays a pivotal role in bone resorption and bone homeostasis by modulating NFATc1 in osteoclasts, thereby providing a molecular connection between amino acid intake and skeletal integrity.

scholarly journals Amino Acid Transport Defects in Human Inherited Metabolic Disorders

2019 ◽  
Vol 21 (1) ◽  
pp. 119 ◽  
Author(s):  
Raquel Yahyaoui ◽  
Javier Pérez-Frías
Keyword(s):  
Amino Acid ◽  
Metabolic Disorders ◽  
Strong Association ◽  
Cell Types ◽  
Amino Acid Transporter ◽  
Molecular Defect ◽  
Amino Acid Transporters ◽  
Inherited Disorders ◽  
Laboratory Findings ◽  
Acid Transporter

Amino acid transporters play very important roles in nutrient uptake, neurotransmitter recycling, protein synthesis, gene expression, cell redox balance, cell signaling, and regulation of cell volume. With regard to transporters that are closely connected to metabolism, amino acid transporter-associated diseases are linked to metabolic disorders, particularly when they involve different organs, cell types, or cell compartments. To date, 65 different human solute carrier (SLC) families and more than 400 transporter genes have been identified, including 11 that are known to include amino acid transporters. This review intends to summarize and update all the conditions in which a strong association has been found between an amino acid transporter and an inherited metabolic disorder. Many of these inherited disorders have been identified in recent years. In this work, the physiological functions of amino acid transporters will be described by the inherited diseases that arise from transporter impairment. The pathogenesis, clinical phenotype, laboratory findings, diagnosis, genetics, and treatment of these disorders are also briefly described. Appropriate clinical and diagnostic characterization of the underlying molecular defect may give patients the opportunity to avail themselves of appropriate therapeutic options in the future.

Cell-surface receptor for ecotropic murine retroviruses is a basic amino-acid transporter

Nature ◽  
1991 ◽  
Vol 352 (6337) ◽  
pp. 729-731 ◽  
Author(s):  
Hao Wang ◽  
Michael P. Kavanaugh ◽  
R. Alan North ◽  
David Kabat
Keyword(s):  
Amino Acid ◽  
Cell Surface ◽  
Basic Amino Acid ◽  
Amino Acid Transporter ◽  
Cell Surface Receptor ◽  
Surface Receptor ◽  
Acid Transporter

scholarly journals The coadministration of trehalose dibehenate and monosodium urate crystals promotes an antitumor phenotype in human-derived myeloid cells

2020 ◽  
Author(s):  
Kristel Kodar ◽  
Melanie-Jane McConnell ◽  
JL Harper ◽  
Mattheus Timmer ◽  
Bridget Stocker
Keyword(s):  
Cell Surface ◽  
Myeloid Cells ◽  
Cell Types ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
Human Monocytes ◽  
Monosodium Urate ◽  
Suppressive Phenotype ◽  
Antigen Presenting ◽  
First Time

© 2020 Australian and New Zealand Society for Immunology Inc. Trehalose dibehenate (TDB), a ligand for the macrophage-inducible C-type lectin, has shown promise as an adjuvant for preventative vaccines and also as an anticancer agent in murine assays. The potential for TDB to affect the antitumor immune response of human myeloid cells, however, has not been studied. We investigated the effect of the adjuvants TDB and monosodium urate (MSU) crystals on the protumor or antitumor immune phenotype of human monocytes, macrophages and monocyte-derived dendritic cells (Mo-DCs). TDB treatment alone led to an inflammatory response in all three cell types, which was most pronounced when using human monocytes, with MSU augmenting this response. TDB also decreased cell surface markers associated with a protumorigenic phenotype, with MSU showing some ability to augment this response. Notably, a significant reduction in CD115 was observed for all antigen-presenting cells upon TDB or MSU + TDB treatment. The potential to increase the antigen-presenting capabilities of the myeloid cells was also observed upon treatment with TDB and MSU + TDB, as indicated by the upregulation of cell surface markers such as CD86 for all three cell types and a favorable ratio of interleukin (IL)-12p40 to IL-10 for monocytes stimulated with MSU + TDB. There was no significant production of IL-12p40 by Mo-DC; however, in a mixed lymphocyte assay, MSU + TDB costimulation of Mo-DC led to a significant increase in CD4+ T-cell numbers and in the IL-12p40-to-IL-10 ratio. Taken together, these findings show for the first time the potential of MSU + TDB costimulation to favor a tumor-suppressive phenotype in human-derived myeloid cells.

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