Regulation of DELLA proteins by post-translational modifications

[EN] DELLA proteins are the negative regulators of the gibberellin (GA) signaling pathway. GAs have a pervasive effect on plant physiology, influencing processes that span the entire life cycle of the plant. All the information encoded by GAs, either environmental or developmental in origin, is canalized through DELLAs, which modulate the activity of many transcription factors and transcriptional regulators. GAs unlock the signaling pathway by triggering DELLA polyubiquitination and degradation by the 26S proteasome. Recent reports indicate, however, that there are other pathways that trigger DELLA polyubiquitination and degradation independently of GAs. Moreover, results gathered during recent years indicate that other post-translational modifications (PTMs), namely phosphorylation, SUMOylation and glycosylation, modulate DELLA function. The convergence of several PTMs in DELLA therefore highlights the strict regulation to which these proteins are subject. In this review, we summarize these discoveries and discuss DELLA PTMs from an evolutionary perspective and examine the possibilities these and other post-translational regulations offer to improve DELLA-dependent agronomic traits.The Spanish Ministry of Science and Innovation (PID2019-109925GB-I00 to D.A.) and the European Union (H2020-MSCA-IF-2016-746396 to A.S.-M.). We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).Blanco-Touriñán, N.; Serrano-Mislata, A.; Alabadí Diego, D. (2020). Regulation of DELLA proteins by post-translational modifications. Plant and Cell Physiology. 61(11):1891-1901. https://doi.org/10.1093/pcp/pcaa113S18911901611

Different role of endothelin ETA and ETB receptors and endothelial modulators in diabetes-induced hyperreactivity of the rabbit carotid artery to endothelin-1

The influence of diabetes on regulatory mechanisms and specific receptors implicated in the contractile response of isolated rabbit carotid arteries to endothelin-1 was examined. Endothelin-1 induced a concentration-dependent contraction that was greater in arteries from diabetic rabbits than in arteries from control rabbits. Endothelium removal or NG-nitro-L-arginine enhanced contractions in response to endothelin-1 only in control arteries, without modifying the endothelin-1 response in diabetic arteries. Indomethacin, furegrelate (thromboxane A2 inhibitor), or cyclo-(D-Asp-Pro-D-Val-Leu-D-Trp) (BQ-123; endothelin ETA receptor antagonist) inhibited the contractions in response to endothelin-1, the inhibition being greater in diabetic arteries than in control arteries. 2,6-Dimethylpiperidinecarbonyl-g-methyl-Leu-Nin- (methoxycarbonyl)-D-Trp-D-Nle (BQ-788; endothelin ETB receptor antagonist) enhanced the contraction elicited by endothelin-1 in control arteries and displaced to the right the contractile curve for endothelin-1 in diabetic arteries. In summary, diabetes induces hyperreactivity of the rabbit carotid artery to endothelin-1 by a mechanism that at least includes: (1) enhanced activity of muscular endothelin ETA receptors; (2) impairment of endothelin ETB receptor-mediated nitric oxide (NO) release; and (3) enhancement of the production of thromboxane A2

Contribution of endothelin receptors and cyclooxygenase-derivatives to the altered response of the rabbit renal artery to endothelin-1 in diabetes

The influence of diabetes on regulatory mechanisms and specific receptors implicated in the response of isolated rabbit renal artery to endothelin-1 was examined. Endothelin-1 induced a concentration-dependent contraction that was less potent in arteries from diabetic rabbits than in arteries from control rabbits. Endothelium removal or NG-nitro-L-arginine (L-NOARG) enhanced contractions to endothelin-1 either in control and diabetic arteries. Indomethacin inhibited endothelin-1-induced response in control arteries, but enhanced it in diabetic arteries. In contrast to that observed in rubbed and in L-NOARG treated arteries, in the presence of indomethacin the contractile action of endothelin-1 was higher in diabetic arteries than in control arteries. Nimesulide enhanced endothelin-1 contractions both in control and diabetic arteries. Cyclo-(D-Asp-Pro-DVal-Leu-D-Trp) (BQ-123, endothelin ETA receptor antagonist), attenuated endothelin-1 vasoconstriction in control rabbits, while vasoconstriction resulted increased in diabetic rabbits. 2,6-Dimethylpiperidinecarbonyl-γ-Methyl-Leu-Nin-(Methoxycarbonyl)-D-Trp-D-Nle (BQ-788, endothelin ETB receptor antagonist), enhanced the contractile response in control rabbit arteries without modifying this response in diabetic rabbits. In summary, diabetes decreases the sensitivity of the rabbit renal artery to endothelin-1 by decreasing the ratio between vasoconstrictor and vasodilator prostanoids released after activation of endothelin ETA receptors

Transcriptional diversification and functional conservation between DELLA proteins in Arabidopsis

[EN] Plasticity and robustness of signaling pathways partly rely on genetic redundancy, although the precise mechanism that provides functional specificity to the different redundant elements in a given process is often unknown. In Arabidopsis, functional redundancy in gibberellin signaling has been largely attributed to the presence of five members of the DELLA family of transcriptional regulators. Here, we demonstrate that two evolutionarily and functionally divergent DELLA proteins, RGL2 and RGA, can perform exchangeable functions when they are expressed under control of the reciprocal promoter. Furthermore, both DELLA proteins display equivalent abilities to interact with PIF4 and with other bHLH transcription factors with a reported role in the control of cell growth and seed germination. Therefore, we propose that functional diversification of Arabidopsis DELLA proteins has largely relied on changes in their gene expression patterns rather than on their ability to interact with different regulatory partners, model also supported by a clustering analysis of DELLA transcript profiles over a range of organs and growth conditions that revealed specific patterns of expression for each of these genes.We deeply appreciate the help of Marta Trenor and Laura Garcia-Carcel in the initial stages of this work. We also thank Tai-ping Sun (Duke University) and the Arabidpsis Biological Resource Center for seeds, Marta Boter for the pGBKT7 and pGADT7 Gateway vectors, Santiago Elena (IBMCP, CSIC-UPV) for useful comments on the manuscript, and Francois Parcy (IRTSV, CNRS-CEA) for fruitful discussions and hosting MAB. Work in the authors' laboratories is funded by grants BIO2007-60923 and BIO2005-07284 from the Spanish Ministry of Science and Innovation. J.G.B. is the recipient of a CSIC I3P Fellowship and J.A.M. is the recipient of a Fellowship from the Fundacion "la Caixa.Gallego-Bartolome, J.; Minguet, E.; Marin, JA.; Prat, S.; Blazquez Rodriguez, MA.; Alabadí Diego, D. (2010). Transcriptional diversification and functional conservation between DELLA proteins in Arabidopsis. Molecular Biology and Evolution. 27(6):1247-1256. https://doi.org/10.1093/molbev/msq0121247125627

TCP14 and TCP15 mediate the promotion of seed germination by gibberellins in Arabidopsis thaliana

Resentini, F.; Felipo-Benavent, A.; Colombo, L.; Blazquez Rodriguez, MA.; Alabadí Diego, D.; Masiero, S. (2015). TCP14 and TCP15 mediate the promotion of seed germination by gibberellins in Arabidopsis thaliana. Molecular Plant. 8(3):482-485. doi:10.1016/j.molp.2014.11.018S4824858

Differential growth at the apical hook: all roads lead to auxin

[EN] The apical hook is a developmentally regulated structure that appears in dicotyledonous seedlings when seeds germinate buried in the soil. It protects the shoot apical meristem and cotyledons from damage while the seedling is pushing upwards seeking for light, and it is formed by differential cell expansion between both sides of the upper part of the hypocotyl. Its apparent simplicity and the fact that it is dispensable when seedlings are grown in vitro have converted the apical hook in one of the favorite experimental models to study the regulation of differential growth. The involvement of hormones especially auxin in this process was manifested already in the early studies. Remarkably, a gradient of this hormone across the hook curvature is instrumental to complete its development, similar to what has been proposed for other processes involving the bending of an organ, such as tropic responses. In agreement with this, other hormones-mainly gibberellins and ethylene-and the light, regulate in a timely and interconnected manner the auxin gradient to promote hook development and its opening, respectively. Here, we review the latest findings obtained mainly with the apical hook of Arabidopsis thaliana, paying special attention to the molecular mechanisms for the cross-regulation between the different hormone signaling pathways that underlie this developmental process.This work was supported by grants from the Spanish Ministry of Science and Innovation (BIO2010-15071 and CSD2007-00057) and the Generalitat Valenciana (ACOMP/2011/288 and PROMETEO/2010/020).Abbas, M.; Alabadí Diego, D.; Blazquez Rodriguez, MA. (2013). Differential growth at the apical hook: all roads lead to auxin. Frontiers in Plant Science. 4:441-1-441-9. https://doi.org/10.3389/fpls.2013.00441S441-1441-9

Mechanisms underlying diabetes enhancement of endothelin-1-induced contraction in rabbit basilar artery

The influence of alloxan-induced diabetes on the reactivity of rabbit basilar artery to endothelin-1 was examined. Endothelin-1 induced concentration-dependent contraction of basilar arteries that was higher in diabetic than in control rabbits. Endothelium removal produced a higher enhancement of the endothelin-1-induced contraction in control than in diabetic rabbits. NG-nitro-L-arginine (L-NOArg) enhanced the maximal contraction induced by endothelin-1 in control rabbits and potentiated this response in diabetic rabbits. Endothelin ETA receptor antagonist, cyclo(D-Asp-Pro-D-Val-Leu-D-Trp) (BQ-123), inhibited endothelin-1-induced contraction in both rabbit groups. Endothelin ETB receptor antagonist, 2,6-Dimethylpiperidinecarbonyl-g-Methyl Leu-Nin-(Methoxycarbonyl)-D-Trp-D-Nle (BQ-788), enhanced endothelin-1-induced contraction in control rabbits and decreased the potency of endothelin-1 in diabetic rabbits. Sodium nitroprusside-induced relaxation of basilar arteries was lower in diabetic than in control rabbits. These results suggest that mechanisms underlying rabbit basilar artery hyperreactivity to endothelin-1 include decreased endothelial modulation of endothelin-1-induced contraction, with impaired endothelial endothelin ETB receptor activity; decreased sensitivity to nitric oxide (NO) in vascular smooth muscle; and enhanced participation of muscular endothelin ETA and ETB receptors

Diabetes potentiates acetylcholine-induced relaxation in rabbit renal arteries

The response of rabbit renal arteries to acetylcholine and its endothelial modulation in diabetes were investigated. Acetylcholine induced concentration-related endothelium-dependent relaxation of renal arteries that was significantly more potent in diabetic rabbits than in control rabbits. Pretreatment with NG-nitro-L-arginine L-NOArg., indomethacin, or L-NOArg plus indomethacin induced partial inhibition of acetylcholine-induced relaxation. Inhibition induced by L-NOArg plus indomethacin was significantly higher in arteries from diabetic rabbits than in arteries from control rabbits. In renal arteries depolarised with KCl 30 mM and incubated with L-NOArg plus indomethacin, acetylcholine-induced relaxation was almost abolished in both groups of rabbits and this response was not different from that obtained in arteries without endothelium. Sodium nitroprusside induced concentration-dependent relaxation of renal arteries from control and diabetic rabbits without significant differences between the two groups of animals. These results suggest that diabetes potentiates the acetylcholine-induced relaxation in rabbit renal arteries. Increased release of nitric oxide and prostacyclin could be responsible for the enhanced relaxant potency of acetylcholine in diabetes

Diabetes-induced changes in endothelial mechanisms implicated in rabbit carotid arterial response to 5-hydroxytryptamine

The influence of diabetes on endothelial mechanisms implicated in the response of isolated rabbit carotid arteries to 5-hydroxytryptamine (5-HT)was studied. 5-HT induced a concentrationdependent contraction that was potentiated in arteries from diabetic rabbits with respect to that in arteries from control rabbits. Endothelium removal potentiated 5-HT contractions in arteries from both control and diabetic rabbits but increased the maximum effect only in arteries from diabetic rabbits. Incubation of arterial segments with Nº-nitro-L-arginine(L-NA)enhanced the contractile response to 5-HT. This L-NA enhancement was greater in arteries from diabetic rabbits than in arteries from control rabbits. Aminoguanidine did not modify the 5-HT contraction in arteries from control and diabetic rabbits. Indomethacin inhibited the 5-HT-induced response, and this inhibition was higher in arteries from control rabbits than in arteries from diabetic rabbits. In summary, diabetes enhances the sensitivity of the rabbit carotid artery to 5-HT. In control animals, the endothelium modulated the arterial response to 5-HT by the release of both nitric oxide (NO) and a vasoconstrictor prostanoid. Diabetes enhances endothelial constitutive NO activity and impairs the production of the endothelial vasoconstricto

Experimental diabetes induces hyperreactivity of rabbit renal artery to 5-hydroxytryptamine

The influence of diabetes on the response of isolated rabbit renal arteries to 5-hydroxytryptamine (5-HT) was examined. 5-HT induced a concentration-related contraction that was higher in arteries from diabetic rabbits than in arteries from control rabbits. Endothelium removal did not significantly modify 5-HT contractions in arteries from control rabbits but enhanced the response to 5-HT in arteries from diabetic rabbits. Incubation with NG-nitro-L-arginine (L-NA) enhanced contractions to 5-HT in arteries from control and diabetic rabbits. In arteries with endothelium, this L-NA enhancement was lower in diabetic rabbits than in control rabbits. In arteries without endothelium, incubation with L-NA enhanced the maximal contractions to 5-HT in control rabbits but did not in diabetic rabbits. Indomethacin inhibited 5-HT-induced contraction of arteries from control rabbits and enhanced the maximal contraction to 5-HT of arteries from diabetic rabbits. In summary, diabetes enhances contractile response of rabbit renal artery to 5-HT. In control animals, this response is regulated by both endothelial and non-endothelial (neuronal) nitric oxide (NO) and by a vasoconstrictor prostanoid. Diabetes impairs the release of non-endothelial NO and the vasoconstrictor prostanoi