scholarly journals Identification of a transporter complex responsible for the cytosolic entry of nitrogen-containing bisphosphonates

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Zhou Yu ◽  
Lauren E Surface ◽  
Chong Yon Park ◽  
Max A Horlbeck ◽  
Gregory A Wyant ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Mevalonate Pathway ◽  
Fluid Phase ◽  
Molecular Target ◽  
Solute Carrier Family ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Genome Wide ◽  
Fluid Phase Endocytosis ◽  
Solute Carrier

Nitrogen-containing-bisphosphonates (N-BPs) are a class of drugs widely prescribed to treat osteoporosis and other bone-related diseases. Although previous studies have established that N-BPs function by inhibiting the mevalonate pathway in osteoclasts, the mechanism by which N-BPs enter the cytosol from the extracellular space to reach their molecular target is not understood. Here, we implemented a CRISPRi-mediated genome-wide screen and identified SLC37A3 (solute carrier family 37 member A3) as a gene required for the action of N-BPs in mammalian cells. We observed that SLC37A3 forms a complex with ATRAID (all-trans retinoic acid-induced differentiation factor), a previously identified genetic target of N-BPs. SLC37A3 and ATRAID localize to lysosomes and are required for releasing N-BP molecules that have trafficked to lysosomes through fluid-phase endocytosis into the cytosol. Our results elucidate the route by which N-BPs are delivered to their molecular target, addressing a key aspect of the mechanism of action of N-BPs that may have significant clinical relevance.

scholarly journals Identification and characterization of a transporter complex responsible for the cytosolic entry of nitrogen-containing-bisphosphonates

2018 ◽  
Author(s):  
Zhou Yu ◽  
Lauren E. Surface ◽  
Chong Yon Park ◽  
Max A. Horlbeck ◽  
Gregory A. Wyant ◽  
...  
Keyword(s):  
Mevalonate Pathway ◽  
Fluid Phase ◽  
Molecular Target ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Genome Wide ◽  
Fluid Phase Endocytosis ◽  
Solute Carrier ◽  
Identification And Characterization

AbstractNitrogen-containing-bisphosphonates (N-BPs) are a class of drugs widely prescribed to treat osteoporosis and other bone-related diseases. Although previous studies have established that N-BPs function by inhibiting the mevalonate pathway in osteoclasts, the mechanism by which N-BPs enter the cytosol from the extracellular space to reach their molecular target is not understood. Here we implemented a CRISPRi-mediated genome-wide screen and identified SLC37A3 (solute carrier family 37 member A3) as a gene required for the action of N-BPs. We observed that SLC37A3 forms a complex with ATRAID (all-trans retinoic acid-induced differentiation factor), a previously identified genetic target of N-BPs. SLC37A3 and ATRAID localize to lysosomes and are required for releasing N-BP molecules that have trafficked to lysosomes through fluid-phase endocytosis into the cytosol. Our results elucidate the route by which N-BPs are delivered to their molecular target, addressing a key aspect of the mechanism of action of N-BPs that may have significant clinical relevance.

scholarly journals Genome-wide genetic structure and selection signatures for color in 10 traditional Chinese yellow-feathered chicken breeds

2020 ◽  
Author(s):  
Xunhe Huang ◽  
Newton O. Otecko ◽  
Minsheng Peng ◽  
Zhuoxian Weng ◽  
Weina Li ◽  
...  
Keyword(s):  
Genetic Structure ◽  
Population Genomics ◽  
Biochemical Properties ◽  
Conservation Strategies ◽  
Potential Candidate ◽  
Solute Carrier Family ◽  
Indigenous Chicken ◽  
Genome Wide ◽  
Yellow Color ◽  
Solute Carrier

Abstract Background: Yellow-feathered chickens (YFCs) have a long history in China. They are well-known for the nutritional and commercial importance attributable to their yellow color phenotype. Currently, there is a huge paucity in knowledge of the genetic determinants responsible for phenotypic and biochemical properties of these iconic chickens. This study aimed to uncover the genetic structure and the molecular underpinnings of the YFCs trademark coloration. Results: The whole-genomes of 100 YFCs from 10 major traditional breeds and 10 Huaibei partridge chickens from China were re-sequenced. Comparative population genomics based on autosomal single nucleotide polymorphisms (SNPs) revealed three geographically based clusters among the YFCs. Compared to other Chinese indigenous chicken genomes incorporated from previous studies, a closer genetic proximity within YFC breeds than between YFC breeds and other chicken populations is evident. Through genome-wide scans for selective sweeps, we identified RALY heterogeneous nuclear ribonucleoprotein (RALY), leucine rich repeat containing G protein-coupled receptor 4 ( LGR4 ), solute carrier family 23 member 2 ( SLC23A2 ), and solute carrier family 2 member 14 ( SLC2A14 ), besides the classical beta-carotene dioxygenase 2 ( BCDO2 ), as major candidates pigment determining genes in the YFCs. Conclusion: We provide the first comprehensive genomic data of the YFCs. Our analyses show phylogeographical patterns among the YFCs and potential candidate genes giving rise to the yellow color trait of the YFCs. This study lays the foundation for further research on the genome-phenotype cross-talks that define important poultry traits and for formulating genetic breeding and conservation strategies for the YFCs.

scholarly journals Genome-wide genetic structure and selection signatures for color in 10 traditional Chinese yellow-feathered chicken breeds

2020 ◽  
Author(s):  
Xunhe Huang ◽  
Newton O. Otecko ◽  
Minsheng Peng ◽  
Zhuoxian Weng ◽  
Weina Li ◽  
...  
Keyword(s):  
Genetic Structure ◽  
Population Genomics ◽  
Biochemical Properties ◽  
Conservation Strategies ◽  
Potential Candidate ◽  
Solute Carrier Family ◽  
Indigenous Chicken ◽  
Genome Wide ◽  
Yellow Color ◽  
Solute Carrier

Abstract Background: Yellow-feathered chickens (YFCs) have a long history in China. They are well-known for the nutritional and commercial importance attributable to their yellow color phenotype. Currently, there is a huge paucity in knowledge of the genetic determinants responsible for phenotypic and biochemical properties of these iconic chickens. This study aimed to uncover the genetic structure and the molecular underpinnings of the YFCs trademark coloration.Results: The whole-genomes of 100 YFCs from 10 major traditional breeds and 10 Huaibei partridge chickens from China were re-sequenced. Comparative population genomics based on autosomal single nucleotide polymorphisms (SNPs) revealed three geographically based clusters among the YFCs. Compared to other Chinese indigenous chicken genomes incorporated from previous studies, a closer genetic proximity within YFC breeds than between YFC breeds and other chicken populations is evident. Through genome-wide scans for selective sweeps, we identified RALY heterogeneous nuclear ribonucleoprotein (RALY), leucine rich repeat containing G protein-coupled receptor 4 (LGR4), solute carrier family 23 member 2 (SLC23A2), and solute carrier family 2 member 14 (SLC2A14), besides the classical beta-carotene dioxygenase 2 (BCDO2), as major candidates pigment determining genes in the YFCs.Conclusion: We provide the first comprehensive genomic data of the YFCs. Our analyses show phylogeographical patterns among the YFCs and potential candidate genes giving rise to the yellow color trait of the YFCs. This study lays the foundation for further research on the genome-phenotype cross-talks that define important poultry traits and for formulating genetic breeding and conservation strategies for the YFCs.

scholarly journals Assignment of solute carrier family 2 (facilitated glucose transporter), members <i>SLC2A2</i>, <i>SLC2A3</i>, <i>SLC2A5</i>, <i>SLC2A8</i> and <i>SLC2A12</i> to porcine chromosomes by somatic cell and radiation hybrid panel mapping (Brief report)

2007 ◽  
Vol 50 (1) ◽  
pp. 114-115
Author(s):  
K. Liu ◽  
S. Zhao ◽  
B. Liu ◽  
B. Fan ◽  
C. Li ◽  
...  
Keyword(s):  
Somatic Cell ◽  
Radiation Hybrid ◽  
Mammalian Cells ◽  
Somatic Cell Hybrid ◽  
Glucose Transporter ◽  
Radiation Hybrid Panel ◽  
Somatic Cell Hybrid Panel ◽  
Solute Carrier Family ◽  
Hydrophilic Character ◽  
Solute Carrier

Abstract. The transport of glucose plays an important role in cellular glucose homeostasis and metabolism [1]. Due to the hydrophilic character of glucose, the transport of glucose in and out of cells requires specific carrier proteins. The mammalian facilitative glucose transport family, which contains the energy-independent transporters (gene symbol SLC2A, protein symbol GLUT), catalyzes the entry of glucose into mammalian cells by facilitative diffusion down a concentration gradient. Thirteen members of mammalian GLUT family have been now characterized [1]. In swine, the chromosomal locations for the five genes (SLC2A2, SLC2A3, SLC2A5, SLC2A8 and SLC2A12) have not yet been determined. In this study, as the first step to better understand of the roles of these GLUTs in pigs which could subsequently be beneficial for pig production, we report the mapping of the five genes using both porcine somatic cell hybrid panel (INRA-SCHP) and radiation hybrid panel (IMpRH).

Molecular Mobility in Trehalose Loaded Mammalian Cells: Time-Resolved Fluorescence Anisotropy Measurements

2008 ◽  
Author(s):  
Nilay Chakraborty ◽  
Wesley Parker ◽  
Kevin E. Elliott ◽  
Stuart T. Smith ◽  
Patrick J. Moyer ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Fluid Phase ◽  
Water Soluble ◽  
Great Promise ◽  
Time Resolved ◽  
Intracellular Space ◽  
Membrane Pores ◽  
Fluid Phase Endocytosis ◽  
Membrane Bound ◽  
Cellular Compartments

Many preservation methods have utilized sugars such as trehalose as protectants against injury during cell preservation processing, especially during drying (1–5). As mammalian cells do not synthesize trehalose, research in the mammalian cell desiccation field has focused on the development of strategies to enable trehalose delivery into the intracellular milieu. Numerous techniques have been explored ranging from microinjection (2) to the creation or utilization of membrane pores (1,3). Fluid phase endocytosis has shown great promise as an effective strategy for non-invasively delivering water-soluble materials into the intracellular space (4, 5). In this technique trehalose is transported across the cell membrane in membrane-bound cellular compartments called endosomes. Cells incubated in cell culture medium containing trehalose have been shown to take up considerable amounts of trehalose by this technique (4, 5). How much of this trehalose actually become available for protection of biomolecules during the dehydration process has yet to be determined.

scholarly journals Genome-wide genetic structure and selection signatures for color in 10 traditional Chinese yellow-feathered chicken breeds

2020 ◽  
Author(s):  
Xunhe Huang ◽  
Newton O. Otecko ◽  
Minsheng Peng ◽  
Zhuoxian Weng ◽  
Weina Li ◽  
...  
Keyword(s):  
Genetic Structure ◽  
Population Genomics ◽  
Biochemical Properties ◽  
Conservation Strategies ◽  
Potential Candidate ◽  
Solute Carrier Family ◽  
Indigenous Chicken ◽  
Genome Wide ◽  
Yellow Color ◽  
Solute Carrier

Abstract Background: Yellow-feathered chickens (YFCs) have a long history in China. They are well-known for the nutritional and commercial importance attributable to their yellow color phenotype. Currently, there is a huge paucity in knowledge of the genetic determinants responsible for phenotypic and biochemical properties of these iconic chickens. This study aimed to uncover the genetic structure and the molecular underpinnings of the YFCs trademark coloration. Results: The whole-genomes of 100 YFCs from 10 major traditional breeds and 10 Huaibei partridge chickens from China were re-sequenced. Comparative population genomics based on autosomal single nucleotide polymorphisms (SNPs) revealed three geographically based clusters among the YFCs. Compared to other Chinese indigenous chicken genomes incorporated from previous studies, a closer genetic proximity within YFC breeds than between YFC breeds and other chicken populations is evident. Through genome-wide scans for selective sweeps, we identified RALY heterogeneous nuclear ribonucleoprotein (RALY), leucine rich repeat containing G protein-coupled receptor 4 ( LGR4 ), solute carrier family 23 member 2 ( SLC23A2 ), and solute carrier family 2 member 14 ( SLC2A14 ), besides the classical beta-carotene dioxygenase 2 ( BCDO2 ), as major candidates pigment determining genes in the YFCs. Conclusion: We provide the first comprehensive genomic data of the YFCs. Our analyses show phylogeographical patterns among the YFCs and potential candidate genes giving rise to the yellow color trait of the YFCs. This study lays the foundation for further research on the genome-phenotype cross-talks that define important poultry traits and for formulating genetic breeding and conservation strategies for the YFCs.

Novel method for isolating mammalian cells defective in fluid-phase endocytosis

1992 ◽  
Vol 18 (6) ◽  
pp. 543-551 ◽  
Author(s):  
Ru-Hung Wang ◽  
Penelope A. Colbaugh ◽  
Peter Kuo ◽  
Mu-Yeh Bau ◽  
Lisa M. Poppe ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Fluid Phase ◽  
Fluid Phase Endocytosis ◽  
Novel Method

scholarly journals Genome-wide genetic structure and selection signatures for color in 10 traditional Chinese yellow-feathered chicken breeds

2020 ◽  
Author(s):  
Xunhe Huang ◽  
Newton O. Otecko ◽  
Minsheng Peng ◽  
Zhuoxian Weng ◽  
Weina Li ◽  
...  
Keyword(s):  
Genetic Structure ◽  
Population Genomics ◽  
Biochemical Properties ◽  
Conservation Strategies ◽  
Potential Candidate ◽  
Solute Carrier Family ◽  
Indigenous Chicken ◽  
Genome Wide ◽  
Yellow Color ◽  
Solute Carrier

Abstract Background: Yellow-feathered chickens (YFCs) have a long history in China. They are well-known for the nutritional and commercial importance attributable to their yellow color phenotype. Currently, there is a huge paucity in knowledge of the genetic determinants responsible for phenotypic and biochemical properties of these iconic chickens. This study aimed to uncover the genetic structure and the molecular underpinnings of the YFCs trademark coloration.Results: The whole-genomes of 100 YFCs from 10 major traditional breeds and 10 Huaibei partridge chickens from China were re-sequenced. Comparative population genomics based on autosomal single nucleotide polymorphisms (SNPs) revealed three geographically based clusters among the YFCs. Compared to other Chinese indigenous chicken genomes incorporated from previous studies, a closer genetic proximity within YFC breeds than between YFC breeds and other chicken populations is evident. Through genome-wide scans for selective sweeps, we identified RALY heterogeneous nuclear ribonucleoprotein (RALY), leucine rich repeat containing G protein-coupled receptor 4 (LGR4), solute carrier family 23 member 2 (SLC23A2), and solute carrier family 2 member 14 (SLC2A14), besides the classical beta-carotene dioxygenase 2 (BCDO2), as major candidates pigment determining genes in the YFCs.Conclusion: We provide the first comprehensive genomic data of the YFCs. Our analyses show phylogeographical patterns among the YFCs and potential candidate genes giving rise to the yellow color trait of the YFCs. This study lays the foundation for further research on the genome-phenotype cross-talks that define important poultry traits and for formulating genetic breeding and conservation strategies for the YFCs.

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