CtBP/BARS is a unique protein family in having quite diversified cellular functions, intercellular localizations, and developmental roles. ANGUSTIFOLIA (AN) is the sole homolog of CtBP/BARS from Arabidopsis thaliana, although it has plant AN-specific motifs and a long C-terminus. Previous studies suggested that AN would function in the nucleus as a transcriptional co-repressor, as CtBPs function in animals; however, precise verification has been lacking. In this paper, we isolated a homologous gene (MAN) of AN from liverwort, Marchantia polymorpha. Transformation of the Arabidopsis an-1 mutant with 35S-driven MAN completely complemented the an-1 phenotype, although it lacks the putative nuclear localization signal (NLS) that exists in AN proteins isolated from other plant species. We constructed several plasmids for expressing modified ANs with amino acid substitutions in known motifs. The results clearly indicated that modified AN with mutations in the putative NLS-like domain could complement the an-1 phenotype. Therefore, we re-examined localization of AN using several techniques. Our results demonstrated that AN localizes on punctuate structures around the Golgi, partially overlapping with a trans-Golgi network resident, which highlighted an unexpected link between leaf development and membrane trafficking. We should reconsider the roles and evolutionary traits of AN based on these findings.
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"KATANIN1 (KTN1), SPIKE1 (SPK1), ZWICHEL (ZWI), ETHYLENE RECEPTOR2 (ETR2), KIESEL (KIS), and PORCINO (POR) participate in microtubule biogenesis (Oppenheimer et al., 1997; Burk et al., 2001; G.T. Kim et al., 2002; Kirik et al., 2002; Qiu et al., 2002; Plett et al., 2009). ANGUSTIFOLIA (AN) localizes to punctate structures around the Golgi apparatus (Minamisawa et al., 2011) and is thought to regulate Golgi-related processes (Hülskamp, 2004), whereas STOMATAL CYTOKINESIS-DEFECTIVE 1 (SCD1) regulates cytokinesis (Falbel et al., 2003; Kang et al., 2003). In addition to these genes, STICHEL (STI) initiates trichome branch formation in a dose-dependent manner via an unknown mechanism (Ilgenfritz et al., 2003; Kasili et al., 2011). "
[Show abstract][Hide abstract] ABSTRACT: The highly elongated single-celled cotton fibre consists of lint and fuzz, similar to the Arabidopsis trichome. Endoreduplication is an important determinant in Arabidopsis trichome initiation and morphogenesis. Fibre development is also controlled by functional homologues of Arabidopsis trichome patterning genes, although fibre cells do not have a branched shape like trichomes. The identification and characterization of the homologues of 10 key Arabidopsis trichome branching genes in Gossypium arboreum are reported here. Nuclear ploidy of fibres was determined, and gene function in cotton callus and fibre cells was investigated. The results revealed that the nuclear DNA content was constant in fuzz, whereas a limited and reversible change occurred in lint after initiation. Gossypeum arboreum BRANCHLESS TRICHOMES (GaBLT) was not transcribed in fibres. The homologue of STICHEL (STI), which is essential for trichome branching, was a pseudogene in Gossypium. Targeted expression of GaBLT, Arabidopsis STI, and the cytokinesis-repressing GaSIAMESE in G. hirsutum fibre cells cultured in vitro resulted in branching. The findings suggest that the distinctive developmental mechanism of cotton fibres does not depend on endoreduplication. This important component may be a relic function that can be activated in fibre cells.
"CtBP is well conserved, and forms of CtBP are expressed from men to flies, worms, and plants [118, 128, 129]. Consistent with its role in tissue morphogenesis, first demonstrated in drosophila, several studies have identified a role for CtBP in driving mammalian epithelial programming where the cellular adhesion molecule E-cadherin is a major target of repression through the recruitment of CtBP/ZEB complexes to multiple E-box transcription factor binding sites (TFBS) in the E-cadherin (CHD1) promoter . "
[Show abstract][Hide abstract] ABSTRACT: The prevalence of obesity has given rise to significant global concerns as numerous population-based studies demonstrate an incontrovertible association between obesity and breast cancer. Mechanisms proposed to account for this linkage include exaggerated levels of carbohydrate substrates, elevated levels of circulating mitogenic hormones, and inflammatory cytokines that impinge on epithelial programming in many tissues. Moreover, recently many scientists have rediscovered the observation, first described by Otto Warburg nearly a century ago, that most cancer cells undergo a dramatic metabolic shift in energy utilization and expenditure that fuels and supports the cellular expansion associated with malignant proliferation. This shift in substrate oxidation comes at the cost of sharp changes in the levels of the high energy intermediate, nicotinamide adenine dinucleotide (NADH). In this review, we discuss a novel example of how shifts in the concentration and flux of substrates metabolized and generated during carbohydrate metabolism represent components of a signaling network that can influence epigenetic regulatory events in the nucleus. We refer to this regulatory process as "metabolic transduction" and describe how the C-terminal binding protein (CtBP) family of NADH-dependent nuclear regulators represents a primary example of how cellular metabolic status can influence epigenetic control of cellular function and fate.
International Journal of Cell Biology 05/2013; 2013(1075):647975. DOI:10.1155/2013/647975
"In addition, the microarray analysis has indicated that several genes were expressed at higher levels in angustifolia mutant plants than in wild type , suggesting that ANGUSTIFOLIA may regulate leaf morphogenesis and other biological processes (i.e., association with microtubule cytoskeleton and by transcriptional regulation). In contrast, recent findings suggest that ANGUSTIFOLIA functions outside the nucleus to control cell morphogenesis . This intriguing finding  and previously reported data could co-exist if ANGUSTIFOLIA employs two different molecular mechanisms: one to control cell morphology and the other, biological functions, respectively. "
[Show abstract][Hide abstract] ABSTRACT: Background
ANGUSTIFOLIA (AN), one of the CtBP family proteins, plays a major role in microtubule-dependent cell morphogenesis. Microarray analysis of mammalian AN homologs suggests that AN might function as a transcriptional activator and regulator of a wide range of genes. Genetic characterization of AN mutants suggests that AN might be involved in multiple biological processes beyond cell morphology regulation.
Using a reverse genetic approach, we provide in this paper the genetic, biochemical, and physiological evidence for ANGUSTIFOLIA’s role in other new biological functions such as abiotic and biotic stress response in higher plants. The T-DNA knockout an-t1 mutant exhibits not only all the phenotypes of previously described angustifolia null mutants, but also copes better than wild type under dehydration and pathogen attack. The stress tolerance is accompanied by a steady-state modulation of cellular H2O2 content, malondialdehyde (MDA) derived from cellular lipid peroxidation, and over-expression of stress responsive genes. Our results indicate that ANGUSTIFOLIA functions beyond cell morphology control through direct or indirect functional protein interaction networks mediating other biological processes such as drought and pathogen attacks.
Our results indicate that the ANGUSTIFOLIA gene participates in several biochemical pathways controlling cell morphogenesis, abiotic, and biotic stress responses in higher plants. Our results suggest that the in vivo function of plant ANGUSTIFOLIA has been overlooked and it needs to be further studied beyond microtubule-dependent cell morphogenesis.