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Two abcI family transporters,OsabcI15 and OsabcI16,are involved in grain-filling in rice

Journal of Genetics and Genomics 2024年第5期51卷 492-506页

作者： Bin Ma Xiubiao Cao Xiaoyuan Li Zhong Bian Qi-Qi Zhang Zijun Fang Jiyun Liu Qun Li Qiaoquan Liu Lin Zhang Zuhua He Jiangsu Key Laboratory of Crop Genomics and Molecular Breeding/Zhongshan Biological Breeding Laboratory/Key Laboratory of Plant Functional Genomics of the Ministry of Education/Jiangsu Key Laboratory of Crop Genetics and Physiology Agricultural College of Yangzhou UniversityYangzhouJiangsu 225009China Jiangsu Co-Innovation Center for Modern Production Technology of Grain Crops Jiangsu Key Laboratory of Crop Genetics and PhysiologyYangzhou UniversityYangzhouJiangsu 225009China National Key Laboratory of Plant Molecular Genetics CAS Center for Excellence in Molecular Plant SciencesInstitute of Plant Physiology&EcologyChinese Academy of SciencesShanghai 200032China Institute of Biotechnology Hangzhou Academy of Agricultural SciencesHangzhouZhejiang 310024China Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education Yangzhou UniversityYangzhouJiangsu 225009China

Seed development is critical for plant reproduction and crop yield,with panicle seed-setting rate,grain-filling,and grain weight being key seed characteristics for yield improvement.However,few genes are known to regulate grain filling.Here,we identify two adenosine triphosphate(ATP)-binding cassette(abc)I-type transporter genes,OsabcI15 and OsabcI16,involved in rice grain-filling.Both genes are highly expressed in developing seeds,and their proteins are localized to the plasma membrane and cytosol.Interestingly,knockout of OsabcI15 and OsabcI16 results in a significant reduction in seed-setting rate,caused predominantly by the severe empty pericarp phenotype,which differs from the previously reported low seed-setting phenotype resulting from failed pollination.Further analysis indicates that OsabcI15 and OsabcI16 participate in ion homeostasis and likely export ions between filial tissues and maternal tissues during grain filling.Importantly,overexpression of OsabcI15 and OsabcI16 enhances the seed-setting rate and grain yield in transgenic plants and decreases ion accumulation in brown rice.Moreover,the OsabcI15/16 orthologues in maize exhibit a similar role in kernel development,as demonstrated by their disruption in transgenic maize.Therefore,ourﬁndings reveal the important roles of two abc transporters in cereal grain filling,highlighting their value in crop yield improvement.

关键词： abc transporters Rice Grain filling Ion homeostasis Grain yield

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Metabolomic profiles in a green alga (Raphidocelis subcapitata) following erythromycin treatment: abc transporters and energy metabolism

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Journal of Environmental Sciences 2023年第2期124卷 591-601页

作者： Jiezhang Mo Zhihua Ma Shiwei Yan Napo KM Cheung Fangshe Yang Xiunan Yao Jiahua Guo Shaanxi Key Laboratory of Earth Surface System and Environmental Carrying Capacity College of Urban and Environmental SciencesNorthwest UniversityXi’an 710127China State Key Laboratory of Marine Pollution and Department of Chemistry City University of Hong KongKowloonHong KongChina

A recent study showed that erythromycin(ERY)exposure caused hormesis in a model alga(Raphidocelis subcapitata)where the growth was promoted at an environmentally realistic concentration(4μg/L)but inhibited at two higher concentrations(80 and 120μg/L),associated with opposite actions of certain signaling pathways(e.g.,xenobiotic metabolism,DNA replication).However,these transcriptional alterations remain to be investigated and verified at the metabolomic level.This study uncovered metabolomic profiles and detailed toxic mechanisms of ERY in R.subcapitata using untargetedmetabolomics.Themetabolomic analysis showed that metabolomic pathways including abc transporters,fatty acid biosynthesis and purine metabolism were associated with growth promotion in algae treated with 4μg/L ERY.An overcompensation was possibly activated by the low level of ERY in algae where more resources were reallocated to efficiently restore the temporary impairments,ultimately leading to the outperformance of growth.By contrast,algal growth inhibition in the 80 and 120μg/L ERY treatments was likely attributed to the dysfunction of metabolomic pathways related to abc transporters,energy metabolism and metabolism of nucleosides.Apart from binding of ERY to the 50S subunit of ribosomes to inhibit protein translation as in bacteria,the data presented here indicate that inhibition of protein translation and growth performance of algae by ERY may also result from the suppression of amino acid biosynthesis and aminoacyl-tRNA biosynthesis.This study provides novel insights into the dose-dependent toxicity of ERY on R.subcapitata.

关键词： Hormesis Metabolome abc transporters DNA replication Microalgae Macrolide antibiotic

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abc transporters and the hallmarks of cancer:roles in cancer aggressiveness beyond multidrug resistance

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Cancer Biology & Medicine 2020年第2期17卷 253-269页

作者： Wanjiru Muriithi Lucy Wanjiku Macharia Carlos Pilotto Heming Juliana Lima Echevarria Atunga Nyachieo Paulo Niemeyer Filho Vivaldo Moura Neto Instituto Estadual do Cerebro Paulo Niemeyer Rio de Janeiro 20231-092Brazil Instituto de Ciencias Biomedicas Universidade Federal do Rio de JaneiroRio de Janeiro 21941-901Brazil institute of Primate Research 24481-00502 NairobiKenya Faculdade de Medicina da Universidade Federal do Rio de Janeiro Rio de Janeiro 21941-901Brazil Instituto de Microbiologia da Universidade Federal do Rio de Janeiro Rio de Janeiro 21941-901Brazil

The ATP-binding cassette transporters(abc transporters)have been intensely studied over the past 50 years for their involvement in the multidrug resistance(MDR)phenotype,especially in cancer.They are frequently overexpressed in both naive and post-treatment tumors,and hinder effective chemotherapy by reducing drug accumulation in cancer cells.In the last decade however,several studies have established that abc transporters have additional,fundamental roles in tumor biology;there is strong evidence that these proteins are involved in transporting tumor-enhancing molecules and/or in protein-protein interactions that impact cancer aggressiveness,progression,and patient prognosis.This review highlights these studies in relation to some well-described cancer hallmarks,in an effort to re-emphasize the need for further investigation into the physiological functions of abc transporters that are critical for tum or development.Unraveling these new roles offers an opportunity to define new strategies and targets for therapy,which would include endogenous substrates or signaling pathways that regulate these proteins.

关键词： abc transporters cancer aggressiveness hallmarks of cancer

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abc transporters,neural stem cells and neurogenesis - a different perspective

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Cell Research 2006年第11期16卷 857-871页

作者： OmedulIslam KlausHeese Department of Molecular and Cell Biology School of Biological Sciences Nanyang Technological University 60 Nanyang Drive Singapore 637551

Stem cells intrigue.They have the ability to divide exponentially,recreate the stem cell compartment,as well as cre-ate differentiated cells to generate tissues.Therefore,they should be natural candidates to provide a renewable sourceof cells for transplantation applied in regenerative medicine.Stem cells have the capacity to generate specific tissues oreven whole organs like the blood,heart,or bones.A subgroup of stem cells,the neural stem cells(NSCs),is characterizedas a self-renewing population that generates neurons and glia of the developing brain.They can be isolated,geneticallymanipulated and differentiated in vitro and reintroduced into a developing,adult or a pathologically altered central nervoussystem.NSCs have been considered for use in cell replacement therapies in various neurodegenerative diseases such asParkinson’s disease and Alzheimer’s disease.Characterization of genes with tightly controlled expression patterns duringdifferentiation represents an approach to understanding the regulation of stem cell commitment.The regulation of stemcell biology by the ATP-binding cassette(abc)transporters has emerged as an important new field of investigation.Asa major focus of stem cell research is in the manipulation of cells to enable differentiation into a targeted cell population;in this review,we discuss recent literatures on abc transporters and stem cells,and propose an integrated view on therole of the abc transporters,especially abcA2,abcA3,abcB1 and abcG2,in NSCs’ proliferation,differentiationand regulation,along with comparisons to that in hematopoietic and other stem cells.

关键词： neural stem cells abc transporters abcB1 abcG2 differentiation stem cell marker

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Thermodynamics of abc transporters

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Protein & Cell 2016年第1期7卷 17-27页

作者： Xuejun C. Zhang Lei Han Yan Zhao National Laboratory of Macromolecules National Center of Protein Science-Beijing Institute of Biophysics Chinese Academyof Sciences Beijing 100101 China

abc transporters form the largest of all transporter families, and their structural study has made tremen- dous progress over recent years. However, despite such advances, the precise mechanisms that determine the energy-coupling between ATP hydrolysis and the con- formational changes following substrate binding remain to be elucidated. Here, we present our thermodynamic analysis for both abc importers and exporters, and introduce the two new concepts of differential-binding energy and elastic conformational energy into the dis- cussion. We hope that the structural analysis of abc transporters will henceforth take thermodynamic aspects of transport mechanisms into account as well.

关键词： abc transporters differential-bindingenergy energy-coupling elastic conformational energy

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abc efflux transporters at blood-central nervous system barriers and their implications for treating spinal cord disorders

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Neural Regeneration Research 2020年第7期15卷 1235-1242页

作者： Liam M. Koehn Department of Pharmacology and Therapeutics the University of Melbourne

The barriers present in the interfaces between the blood and the central nervous system form a major hurdle for the pharmacological treatment of central nervous system injuries and diseases.The family of ATP-binding cassette(abc)transporters has been widely studied regarding efflux of medications at blood-central nervous system barriers.These efflux transporters include P-glycoprotein(abcb1),‘breast cancer resistance protein'(abcg2)and the various‘multidrug resistance-associated proteins'(abccs).Understanding which efflux transporters are present at the blood-spinal cord,blood-cerebrospinal fluid and cerebrospinal fluid-spinal cord barriers is necessary to determine their involvement in limiting drug transfer from blood to the spinal cord tissue.Recent developments in the blood-brain barrier field have shown that barrier systems are dynamic and the profile of barrier defenses can alter due to conditions such as age,disease and environmental challenge.This means that a true understanding of abc efflux transporter expression and localization should not be one static value but instead a range that represents the complex patient subpopulations that exist.In the present review,the blood-central nervous system barrier literature is discussed with a focus on the impact of abc efflux transporters on:(i)protecting the spinal cord from adverse effects of systemically directed drugs,and(ii)limiting centrally directed drugs from accessing their active sites within the spinal cord.

关键词： abc transporters ATP-binding cassette BCRP blood-brain barrier blood-spinal cord barrier efflux MRP P-glycoprotein PGP spinal cord injury

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Plant pleiotropic drug resistance transporters:Transport mechanism, gene expression,and function

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Journal of Integrative Plant Biology 2014年第8期56卷 729-740页

作者： Mohammed Nuruzzaman Ru Zhang Hong-Zhe Cao Zhi-Yong Luo Molecular Biology Research Center School of Life Sciences Central South University State Key Laboratory of Medical Genetics Xiangya School of Medicine Central South University

Pleiotropic drug resistance （PDR） transporters belonging to the abcG subfamily of ATP-binding cassette （abc） transporters are identified only in fungi and plants. Members of this family are expressed in plants in response to various biotic and abiotic stresses and transport a diverse array of moleculesacross membranes, Although their detailed transport mechanism is largely unknown, they play important roles in detoxification processes, preventing water loss, transport of phytohormones, and secondary metabolites. This review provides insights into transport mechanisms of plant PDR transporters, their expression profiles, and multitude functions in plants.

关键词： abc transporters expression pattern plant defense pleiotropic drug resistance transport mechanism

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The roles of the human ATP-binding cassette transporters P-glycoprotein and abcG2 in multidrug resistance in cancer and at endogenous sites: future opportunities for structure-based drug design of inhibitors

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Cancer Drug Resistance 2021年第4期4卷 784-804页

作者： Jason Goebel Jean Chmielewski Christine A.Hrycyna Department of Chemistry Purdue University West LafayetteIN 47907USA

The ATP-binding cassette(abc)transporters P-glycoprotein(P-gp)and abcG2 are multidrug transporters that confer drug resistance to numerous anti-cancer therapeutics in cell culture.These findings initially created great excitement in the medical oncology community,as inhibitors of these transporters held the promise of overcoming clinical multidrug resistance in cancer patients.However,clinical trials of P-gp and abcG2 inhibitors in combination with cancer chemotherapeutics have not been successful due,in part,to flawed clinical trial designs resulting from an incomplete molecular understanding of the multifactorial basis of multidrug resistance(MDR)in the cancers examined.The field was also stymied by the lack of high-resolution structural information for P-gp and abcG2 for use in the rational structure-based drug design of inhibitors.Recent advances in structural biology have led to numerous structures of both abcG2 and P-gp that elucidated more clearly the mechanism of transport and the polyspecific nature of their substrate and inhibitor binding sites.These data should prove useful helpful for developing even more potent and specific inhibitors of both transporters.As such,although possible pharmacokinetic interactions would need to be evaluated,these inhibitors may show greater effectiveness in overcoming abc-dependent multidrug resistance in combination with chemotherapeutics in carefully selected subsets of cancers.Another perhaps even more compelling use of these inhibitors may be in reversibly inhibiting endogenously expressed P-gp and abcG2,which serve a protective role at various blood-tissue barriers.Inhibition of these transporters at sanctuary sites such as the brain and gut could lead to increased penetration by chemotherapeutics used to treat brain cancers or other brain disorders and increased oral bioavailability of these agents,respectively.

关键词： P-glycoprotein abcG2 abc transporters multidrug resistance inhibitor

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ATP-binding cassette transporters at the zebrafish blood-brain barrier and the potential utility of the zebrafish as an in vivo model

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Cancer Drug Resistance 2021年第3期4卷 620-633页

作者： Jordan M.Hotz Joanna R.Thomas Emily N.Katz Robert W.Robey Sachi Horibata Michael M.Gottesman Laboratory of Cell Biology Center for Cancer ResearchNational Cancer InstituteNational Institutes of HealthBethesdaMD 20892USA Zebrafish Core Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentBethesdaMD 20892USA

The brain is protected from toxins by a tightly regulated network of specialized cells,including endothelial cells,pericytes,astrocyes,and neurons,known collectively as the blood-brain barrier(BBB).This selectively permeable barrier permits only the most crucial molecules essential for brain function to enter and employs a number of different mechanisms to prevent the entry of potentially harmful toxins and pathogens.In addition to a physical barrier comprised of endothelial cells that form tight junctions to restrict paracellular transport,there is an active protective mechanism made up of energy-dependent transporters that efflux compounds back into the bloodstream.Two of these ATP-binding cassette(abc)transporters are highly expressed at the BBB:P-glycoprotein(P-gp,encoded by the abcB1 gene)and abcG2(encoded by the abcG2 gene).Although a number of in vitro and in vivo systems have been developed to examine the role that abc transporters play in keeping compounds out of the brain,all have inherent advantages and disadvantages.Zebrafish(Danio rerio)have become a model of interest for studies of the BBB due to the similarities between the zebrafish and mammalian BBB systems.In this review,we discuss what is known about abc transporters in zebrafish and what information is still needed before the zebrafish can be recommended as a model to elucidate the role of abc transporters at the BBB.

关键词： abc transporters blood-brain barrier abcG2 P-glycoprotein zebrafish

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New mechanisms of multidrug resistance: an introduction to the Cancer Drug Resistance special collection

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Cancer Drug Resistance 2023年第3期6卷 590-595页

作者： Michael M.Gottesman Robert W.Robey Suresh V.Ambudkar Laboratory of Cell Biology Center for Cancer ResearchNational Cancer InstituteNational Institutes of HealthBethesdaMD 20892USA

Cancer Drug Resistance publishes contributions to understanding the biology and consequences of mechanisms that interfere with successful treatment of cancer. Since virtually all patients who die of metastatic cancer have multidrug-resistant tumors, improved treatment will require an understanding of the mechanisms of resistance to design therapies that circumvent these mechanisms, exploit these mechanisms, or inactivate these multidrug resistance mechanisms. One example of a resistance mechanism is the expression of ATP-binding cassette efflux pumps, but unfortunately, inhibition of these transporters has not proved to be the solution to overcome multidrug resistance in cancer. Other mechanisms that confer multidrug resistance, and the confluence of multiple different mechanisms (multifactorial multidrug resistance) have been identified, and it is the goal of this Special Collection to expand this catalog of potential multidrug resistance mechanisms, to explore novel ways to overcome resistance, and to present thoughtful reviews on the problem of multidrug resistance in cancer.

关键词： Cancer drug resistance multidrug resistance abc transporters novel mechanisms of drug resistance

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