Increased tolerance to low K+, and to cationic stress of Arabidopsis plants by expressing the F130S mutant version of the K+ transporter AtHAK5.

Potassium (K+) selectivity of high-affinity K+ uptake systems is crucial for plant growth under low K+ and in the presence of inhibitors of K+ uptake that are toxic to plants such as Na+ or Cs+. Here, we express a mutated version of the Arabidopsis AtHAK5 high-affinity K+ transporter consisting on a change of phenylalanine 130 to serine (F130S) in athak5 akt1 double mutant plants. F130S-expressing plants show better growth, increased K+ uptake from low external concentrations and higher K+ contents when grown at low K+ (10 µM) and when grown at low K+ in the presence of Na+ (15 mM) or Cs+ (1 µM). In addition, these plants accumulate less Na+ and Cs+, resulting in lower Na+/K+ and Cs+/K+ ratios, which are important determinants of plant tolerance to salt stress and to Cs+-polluted soils. Structure analysis of AtHAK5 suggest that the F130 residue approaches the intracellular gate of the K+ tunnel of AtHAK5, affecting somehow its ionic selectivity. Modification of transport systems has a large potential to face challenges of future agriculture such as sustainable production under abiotic stress conditions imposed by climate change.

Relevance of the SlCIPK23 kinase in Na+ uptake and root morphology in K+-starved tomato plants.

The beneficial effects of Na+ as a substitute for K+ have been well-documented at the physiological level. However, the transport systems and regulatory mechanisms that allow Na+ acquisition under K+ deficiency remain poorly understood in the majority of land plants. In tomato, SlCIPK23 kinase was involved in Na+ accumulation in K+-starved plants, in addition to activating the LKT1 K+ channel and the K+ transporter SlHAK5. We used the central role of SlCIPK23 in K+ and Na+ acquisition to study which molecular entities mediate Na+ uptake with knockout tomato mutants and expression in heterologous systems. Two main pathways for Na+ uptake were deduced in tomato plants: an NH4+-sensitive pathway dependent on SlCIPK23, and a second one sensitive to Ba2+, Ca2+, La3+, and Li+. The addition of Na+ (10 mM) to lkt1, slhak5, or slcipk23 mutant KO lines produced interesting changes in root morphology. In particular, the roots of slcipk23 plants were longer and lighter than those of the WT under K+-deficient conditions and this effect was reversed by the addition of 10 mM Na+. These results provide a stimulating perspective for the study of the beneficial effects of Na+ in crops.

Inhibition of SlSKOR by SlCIPK23-SlCBL1/9 uncovers CIPK-CBL-target network rewiring in land plants.

Transport of K+ to the xylem is a key process in the mineral nutrition of the shoots. Although CIPK-CBL complexes have been widely shown to regulate K+ uptake transport systems, no information is available about the xylem ones. Here, we studied the physiological roles of the voltage-gated K+ channel SlSKOR and its regulation by the SlCIPK23-SlCBL1/9 complexes in tomato plants. We phenotyped gene-edited slskor and slcipk23 tomato knockout mutants and carried out two-electrode voltage-clamp (TEVC) and BiFC assays in Xenopus oocytes as key approaches. SlSKOR was preferentially expressed in the root stele and was important not only for K+ transport to shoots but also, indirectly, for that of Ca2+ , Mg2+ , Na+ , NO3 - , and Cl- . Surprisingly, the SlCIPK23-SlCBL1/9 complexes turned out to be negative regulators of SlSKOR. Inhibition of SlSKOR by SlCIPK23-SlCBL1/9 was observed in Xenopus oocytes and tomato plants. Regulation of SKOR-like channels by CIPK23-CBL1 complexes was also present in Medicago, grapevine, and lettuce but not in Arabidopsis and saltwater cress. Our results provide a molecular framework for coordinating root K+ uptake and its translocation to the shoot by SlCIPK23-SlCBL1/9 in tomato plants. Moreover, they evidenced that CIPK-CBL-target networks have evolved differently in land plants.

The protein kinase SlCIPK23 boosts K+ and Na+ uptake in tomato plants.

Regulation of root transport systems is essential under fluctuating nutrient supply. In the case of potassium (K+ ), HAK/KUP/KT K+ transporters and voltage-gated K+ channels ensure root K+ uptake in a wide range of K+ concentrations. In Arabidopsis, the CIPK23/CBL1-9 complex regulates both transporter- and channel-mediated root K+ uptake. However, research about K+ homeostasis in crops is in demand due to species-specific mechanisms. In the present manuscript, we studied the contribution of the voltage-gated K+ channel LKT1 and the protein kinase SlCIPK23 to K+ uptake in tomato plants by analysing gene-edited knockout tomato mutant lines, together with two-electrode voltage-clamp experiments in Xenopus oocytes and protein-protein interaction analyses. It is shown that LKT1 is a crucial player in tomato K+ nutrition by contributing approximately 50% to root K+ uptake under K+ -sufficient conditions. Moreover, SlCIPK23 was responsible for approximately 100% of LKT1 and approximately 40% of the SlHAK5 K+ transporter activity in planta. Mg+2 and Na+ compensated for K+ deficit in tomato roots to a large extent, and the accumulation of Na+ was strongly dependent on SlCIPK23 function. The role of CIPK23 in Na+ accumulation in tomato roots was not conserved in Arabidopsis, which expands the current set of CIPK23-like protein functions in plants.

Insights into the mechanisms of transport and regulation of the arabidopsis high-affinity K+ transporter HAK51.

The high-affinity K+ transporter HAK5 from Arabidopsis (Arabidopsis thaliana) is essential for K+ acquisition and plant growth at low micromolar K+ concentrations. Despite its functional relevance in plant nutrition, information about functional domains of HAK5 is scarce. Its activity is enhanced by phosphorylation via the AtCIPK23/AtCBL1-9 complex. Based on the recently published three-dimensionalstructure of the bacterial ortholog KimA from Bacillus subtilis, we have modeled AtHAK5 and, by a mutational approach, identified residues G67, Y70, G71, D72, D201, and E312 as essential for transporter function. According to the structural model, residues D72, D201, and E312 may bind K+, whereas residues G67, Y70, and G71 may shape the selective filter for K+, which resembles that of K+shaker-like channels. In addition, we show that phosphorylation of residue S35 by AtCIPK23 is required for reaching maximal transport activity. Serial deletions of the AtHAK5 C-terminus disclosed the presence of an autoinhibitory domain located between residues 571 and 633 together with an AtCIPK23-dependent activation domain downstream of position 633. Presumably, autoinhibition of AtHAK5 is counteracted by phosphorylation of S35 by AtCIPK23. Our results provide a molecular model for K+ transport and describe CIPK-CBL-mediated regulation of plant HAK transporters.

Pioderma gangrenoso vulvar: revisión de la literatura a propósito de un caso causado por rituximab / Vulvar pyoderma gangrenosum: review of the literature on a case caused by rituximab

RESUMEN El Pioderma Gangrenoso (PG) es una enfermedad inflamatoria necrotizante crónica, que pertenece al espectro de las dermatosis neutrofílicas. Histológicamente se caracteriza por mostrar un infiltrado inflamatorio denso de neutrófilos de origen no infeccioso. El PG suele asociarse a enfermedades sistémicas como la enfermedad inflamatoria intestinal, la artritis reumatoide o diversas enfermedades hematológicas. Presenta fenómeno de patergia y suele responder satisfactoriamente a tratamientos inmunosupresores. Su etiología no está bien definida. En la literatura se han publicado 15 casos de pioderma gangrenoso vulvar asociado al uso de rituximab. Nosotros presentamos un nuevo caso, que tuvo lugar en una mujer de 37 años en tratamiento de mantenimiento con rituximab por un linfoma no Hodgkin folicular. El rituximab (MabThera®) es un anticuerpo que reconoce la molécula CD20, que es una proteína no glucosilada que se expresa en la superficie de los linfocitos B. Este fármaco se ha utilizado para el tratamiento de diferentes enfermedades reumatológicas en los últimos años.

ABSTRACT Pyoderma Gangrenosum is a chronic necrotizing inflammatory disease that belongs to the spectrum of Neutrophilic Dermatoses. Histologically, it is characterized by a dense inflammatory infiltrate of non-infectious neutrophils. Etiology is not yet well defined. It is usually associated with systemic diseases such as inflammatory bowel disease, rheumatoid arthritis or hematological diseases. It presents pathergy phenomenon and usually respond satisfactorily to immunosuppressive treatments. There have been published only 15 cases of vulvar pyoderma gangrenosum associated with the use of rituximab. We present a new case, which occurred in a 37-year-old woman on maintenance treatment with rituximab for a follicular non-Hodgkin's lymphoma. Rituximab (MabThera®) is an antibody that recognizes the CD20 molecule, which is a non-glycosylated protein that is expressed on the surface of B lymphocytes. This drug has been used for the treatment of different rheumatic diseases in recent years.