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1.
Plant Signal Behav ; 18(1): 2164670, 2023 12 31.
Article in English | MEDLINE | ID: mdl-36645916

ABSTRACT

Cell-to-cell communication via membranous channels called plasmodesmata (PD) plays critical roles during plant development and in response to biotic and abiotic stresses. Several enzymes and receptor-like proteins (RLPs), including Arabidopsis thaliana glucan synthase-likes (GSLs), also known as callose synthases (CALSs), and PD-located proteins (PDLPs), have been implicated in plasmodesmal permeability regulation and intercellular communication. Localization of PDLPs to punctate structures at the cell periphery and their receptor-like identity have raised the hypothesis that PDLPs are involved in the regulation of symplastic trafficking during plant development and in response to endogenous and exogenous signals. Indeed, it was shown that PDLP5 could limit plasmodesmal permeability through inducing an increase in callose accumulation at PD. However, mechanistically, how this is achieved remains to be elucidated. To address this key issue in understanding the regulation of PD, physical and functional interactions between PDLPs and GSLs (using the PDLP5-GSL8/CALS10 pair as a model) were investigated. Our results show that GSL8/CALS10 plays essential roles and is required for the function and plasmodesmal localization of PDLP5. Furthermore, it was demonstrated that the localization of PDLP5 to PD and its function in inducing callose deposition are GSL8-dependent. Importantly, our transgenic study shows that three key members of the GSL family, i.e., GSL5/CALS12, GSL8/CALS10, and GSL12/CALS3, localize to PD and co-localize with PDLP5, suggesting that GSL8/CALS10 might not be the only callose synthase with the determining role in PD regulation. These findings, together with our previous observation showing the direct interaction of GSL8/CALS10 with PDLP5, indicate the pivotal role of the GSL8/CALS10-PDLP5 interplay in regulating PD permeability. Future work is needed to investigate whether the PDLP5 functionality and localization are also disrupted in gsl5 and gsl12, or it is just gsl8-specific.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis/metabolism , Arabidopsis Proteins/metabolism , Plasmodesmata/metabolism , Permeability , Membrane Proteins/metabolism
2.
Cancer Rep (Hoboken) ; 5(4): e1351, 2022 04.
Article in English | MEDLINE | ID: mdl-33635590

ABSTRACT

BACKGROUND: Elevated basal cortisol levels are present in women with primary and metastatic breast cancer. Although cortisol's potential role in breast-to-brain metastasis has yet to be sufficiently studied, prior evidence indicates that it functions as a double-edged sword-cortisol induces breast cancer metastasis in vivo, but strengthens the blood-brain-barrier (BBB) to protect the brain from microbes and peripheral immune cells. AIMS: In this study, we provide a novel examination on whether cortisol's role in tumor invasiveness eclipses its supporting role in strengthening the CNS barriers. We expanded our study to include the blood-cerebrospinal fluid barrier (BCSFB), an underexamined site of tumor entry. METHODS AND RESULTS: Utilizing in vitro BBB and BCSFB models to measure barrier strength in the presence of hydrocortisone (HC). We established that lung tumor cells migrate through both CNS barriers equally while breast tumors cells preferentially migrate through the BCSFB. Furthermore, HC treatment increased breast-to-brain metastases (BBM) but not primary breast tumor migratory capacity. When examining the transmigration of breast cancer cells across the BCSFB, we demonstrate that HC induces increased traversal of BBM but not primary breast cancer. We provide evidence that HC increases tightness of the BCSFB akin to the BBB by upregulating claudin-5, a tight junction protein formerly acknowledged as exclusive to the BBB. CONCLUSION: Our findings indicate, for the first time that increased cortisol levels facilitate breast-to-brain metastasis through the BCSFB-a vulnerable point of entry which has been typically overlooked in brain metastasis. Our study suggests cortisol plays a pro-metastatic role in breast-to-brain metastasis and thus caution is needed when using glucocorticoids to treat breast cancer patients.


Subject(s)
Brain Neoplasms , Breast Neoplasms , Neoplasms, Second Primary , Blood-Brain Barrier/metabolism , Brain , Breast Neoplasms/metabolism , Female , Humans , Hydrocortisone/metabolism , Hydrocortisone/pharmacology
3.
Curr Protoc Stem Cell Biol ; 49(1): e80, 2019 06.
Article in English | MEDLINE | ID: mdl-30720927

ABSTRACT

A population of neural stem cells exists in the adult mammalian central nervous system. Purification and characterization of neurospheres provide valuable tools to study the regulation and differentiation of neural stem cells both in vitro and in vivo. Successful stimulation and production of neurospheres can ultimately be used for therapeutic purposes. The currently available methods are limited by their poor yield and the large number of animals required to compensate for that. Here, we describe a procedure to purify neurospheres from adult mouse whole brain. We provide detailed steps on how to propagate, passage, and maintain the adult neurospheres, and how to differentiate the pure neurospheres into the lineage of interest. Using this method, neurospheres can be easily derived from adult mouse whole brain. The derived adult neurospheres maintain their homogenous undifferentiated status while retaining their differentiation potential. This new protocol facilitates adult neurospheres isolation, purification, maintenance, and differentiation. © 2019 by John Wiley & Sons, Inc.


Subject(s)
Brain/cytology , Cell Culture Techniques/methods , Cell Separation/methods , Neural Stem Cells/cytology , Neurons/cytology , Animals , Cells, Cultured , Mice
4.
BMC Plant Biol ; 18(1): 295, 2018 Nov 22.
Article in English | MEDLINE | ID: mdl-30466394

ABSTRACT

BACKGROUND: Plant cell walls are mainly composed of polysaccharides such as cellulose and callose. Callose exists at a very low level in the cell wall; however, it plays critical roles at different stages of plant development as well as in defence against unfavorable conditions. Callose is accumulated at the cell plate, at plasmodesmata and in male and female gametophytes. Despite the important roles of callose in plants, the mechanisms of its synthesis and regulatory properties are not well understood. RESULTS: CALLOSE SYNTHASE (CALS) genes, also known as GLUCAN SYNTHASE-LIKE (GSL), comprise a family of 12 members in Arabidopsis thaliana. Here, we describe a new allele of GSL8 (named essp8) that exhibits pleiotropic seedling defects. Reduction of callose deposition at the cell plates and plasmodesmata in essp8 leads to ectopic endomitosis and an increase in the size exclusion limit of plasmodesmata during early seedling development. Movement of two non-cell-autonomous factors, SHORT ROOT and microRNA165/6, both required for root radial patterning during embryonic root development, are dysregulated in the primary root of essp8. This observation provides evidence for a molecular mechanism explaining the gsl8 root phenotype. We demonstrated that GSL8 interacts with PLASMODESMATA-LOCALIZED PROTEIN 5, a ß-1,3-glucanase, and GSL10. We propose that they all might be part of a putative callose synthase complex, allowing a concerted regulation of callose deposition at plasmodesmata. CONCLUSION: Analysis of a novel mutant allele of GSL8 reveals that GSL8 is a key player in early seedling development in Arabidopsis. GSL8 is required for maintaining the basic ploidy level and regulating the symplastic trafficking. Callose deposition at plasmodesmata is highly regulated and occurs through interaction of different components, likely to be incorporated into a callose biosynthesis complex. We are providing new evidence supporting an earlier hypothesis that GSL8 might have regulatory roles apart from its enzymatic function in plasmodesmata regulation.


Subject(s)
Arabidopsis Proteins/physiology , Arabidopsis/physiology , Cytokinesis , Glucosyltransferases/physiology , Alleles , Arabidopsis/genetics , Arabidopsis/growth & development , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Genetic Pleiotropy , Glucans/metabolism , Glucosyltransferases/genetics , Glucosyltransferases/metabolism , Membrane Proteins/metabolism , Mutation , Plasmodesmata/metabolism , Seedlings/genetics , Seedlings/growth & development
5.
Nat Plants ; 3(10): 814-824, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28947800

ABSTRACT

Acetyl-coenzyme A (acetyl-CoA) is a central metabolite and the acetyl source for protein acetylation, particularly histone acetylation that promotes gene expression. However, the effect of acetyl-CoA levels on histone acetylation status in plants remains unknown. Here, we show that malfunctioned cytosolic acetyl-CoA carboxylase1 (ACC1) in Arabidopsis leads to elevated levels of acetyl-CoA and promotes histone hyperacetylation predominantly at lysine 27 of histone H3 (H3K27). The increase of H3K27 acetylation (H3K27ac) is dependent on adenosine triphosphate (ATP)-citrate lyase which cleaves citrate to acetyl-CoA in the cytoplasm, and requires histone acetyltransferase GCN5. A comprehensive analysis of the transcriptome and metabolome in combination with the genome-wide H3K27ac profiles of acc1 mutants demonstrate the dynamic changes in H3K27ac, gene transcripts and metabolites occurring in the cell by the increased levels of acetyl-CoA. This study suggests that H3K27ac is an important link between cytosolic acetyl-CoA level and gene expression in response to the dynamic metabolic environments in plants.


Subject(s)
Acetyl Coenzyme A/metabolism , Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , Histones/metabolism , Acetyl-CoA Carboxylase/genetics , Acetyl-CoA Carboxylase/metabolism , Acetylation , Cytosol/metabolism , Isoenzymes/genetics , Isoenzymes/metabolism , Lysine/metabolism
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