The yeast two-component SLN1 branch of the HOG pathway and the scaffolding activity of Pbs2 modulate the response to endoplasmic reticulum stress induced by tunicamycin / La rama SLN1 de dos componentes de levadura de la vía HOG y la actividad de andamiaje de Pbs2 modulan la respuesta al estrés del retículo endoplásmico inducido por tunicamicina

In addition to the UPR pathway, yeast cells require components of the HOG pathway to respond to ER stress. In this work, we found that unphosphorylated Sln1 and Ssk1 are required to mount an appropriate response to Tn. We also found that the MAPKKKs Ssk2 participates in the Tn response, but its osmo-redundant protein Ssk22 does not. We also found that the Pbs2 docking sites for Ssk2 (RDS-I and KD) are partially dispensable when mutated separately; however, the prevention of Ssk2 binding to Pbs2, by the simultaneous mutation of RDS-I and KD, caused strong sensitivity to Tn. In agreement with the lack of Hog1 phosphorylation during Tn treatment, a moderate resistance to Tn is obtained when a Pbs2 version lacking its kinase activity is expressed; however, the presence of mutual Pbs2-Hog1 docking sites is essential for the Tn response. Finally, we detected that Tn induced a transcriptional activation of some components of the SLN1 branch. These results indicate that the Tn response requires a complex formed by the MAPK module and components of the SLN1 branch but not their canonical osmoregulatory activities.(AU)

GRP78 and alpha2-macroglobulin are new promising targets for metastatic castrate-resistant prostate cancer treatment

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Inflamación intestinal y estrés de retículos endoplásmico / No disponible

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Unraveling STIM2 function

The discovery of molecular players in capacitative calcium (Ca2+) entry, also referred to as store-operated Ca2+ entry (SOCE), supposed a great advance in the knowledge of cellular mechanisms of Ca2+ entry, which are essential for a broad range of cellular functions. The identification of STIM1 and STIM2 proteins as the sensors of Ca2+ stored in the endoplasmic reticulum unraveled the mechanism by which depletion of intracellular Ca2+ stores is communicated to store-operated Ca2+channels located in the plasma membrane, triggering the activation of SOCE and intracellular Ca2+-dependent signaling cascades. Initial studies suggested a dominant function of STIM1 in SOCE and SOCE-dependent cellular functions compared to STIM2, especially those that participate in immune responses. Consequently, most of the subsequent studies focused on STIM1. However, during the last years, STIM2 has been demonstrated to play a more relevant and complex function than initially reported, being even important to sustain normal life in mice. These studies have led to reconsider the role of STIM2 in SOCE and its relevance in cellular physiology. This review is intended to summarize and provide an overview of the current data available about this exciting isoform, STIM2, and its actual position together with STIM1 in the mechanism of SOCE (AU)

Síndrome metabólico y envejecimiento / Metabolic syndrome and aging

La actual “epidemia de obesidad”, y su correlato, el síndrome metabólico, se ha puesto en relación en los últimos años no solamente con enfermedad cardiovascular, sino con la presencia de múltiples enfermedades crónicas, e incluso con el desarrollo de incapacidad. Por ello, se ha llegado a establecer la hipótesis de que esta situación de riesgo y la situación de fragilidad que tanto interés ha despertado en el ámbito de la Geriatría compartirían mecanism(AU)

In recent years, the current “obesity epidemic” and its correlate, metabolic syndrome, have been related not only to cardiovascular disease but also to the presence of multiple chronic diseases and even to the development of disability. Therefore, it has been hypothesized that this situation of risk and that of frailty, which has aroused such interest in geriatrics, could share common physiopathologic mechanisms. These mechanisms are reviewed in the present article(AU)

Nefrotoxicidad por xenobióticos y agentes biológicos / Nephrotoxixity due to xenobiotics and biological agents

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Reticulohistiocitosis cutánea difusa / Diffuse cutaneous reticulohistiocytosis

Las reticulohistiocitosis constituyen un grupo heterogéneo de enfermedades que tienen su origen en la acumulación de células de estirpe histiocitaria en diferentes tejidos y fundamentalmente en la piel. Se han descrito tres formas clínicas principales (multicéntrica, solitaria, cutánea difusa) que presentan idénticas características histológicas, ultraestructurales e inmunohistoquímicas. Presentamos un caso de reticulohistiocitosis cutánea difusa que constituye el patrón clínico menos común dentro del espectro de esta enfermedad

The reticulohistiocytoses make up a heterogeneous group of diseases whose origin lies in an accumulation of cells of histiocytic lineage in different tissues and primarily in the skin. Three main clinical forms have been described (multicentric, solitary, diffuse cutaneous), which present with identical histological, ultrastructural and immunohistochemical characteristics. We present a case of diffuse cutaneous reticulohistiocytosis, which is the least common clinical pattern in the spectrum of this disease

El tráfico intracelular de colesterol como diana terapéutica / Intracellular cholesterol traffic as a therapeutic target

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Nuevos mecanismos moleculares de la nefrotoxicidad / New molecular mechanisms of nephrotoxicity

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Retículo pigmentado negativo en un nevus melanocítico en crecimiento / Negative pigment networt in a growing melanocytic nevus

Durante el seguimiento de una paciente con múltiples nevus melanocíticos se detectó una lesión pigmentada con crecimiento focal. El examen dermoscópico reveló en el área en crecimiento una zona ligeramente azulada y un sector con un retículo pigmentado negativo. En el diagnóstico diferencial se consideró la posibilidad de melanoma incipiente. El estudio histológico mostró en el área en crecimiento un nevus compuesto con atipia arquitectural pero sin atipia citológica (AU)

Intracellular transport of a heterologous membrane protein, the human transferrin receptor, in Saccharomyces cerevisiae / Transporte intracelular de una proteína de membrana heteróloga, el receptor de transferrina humano, en Saccharomyces cerevisiae

We have analyzed the intracellular behavior of the human transferrin receptor (TfR) in Saccharomyces cerevisiae. The major part of the heterologously expressed TfR, which has previously been used as a model for heterologous expression of membrane proteins in yeast, is localized in the endoplasmic reticulum (ER) membranes; a minor fraction is present in the plasma membrane (PM). The stability of the TfR depends on vacuolar proteases, implying that it is degraded in the vacuolar compartment. Degradation is further dependent on favorable transport conditions to this compartment. The main bottleneck of transport seems to be the transition from the ER to the PM. The chaperone Cne1p, which is involved in quality control in the ER, plays a role in regulating the amount of heterologous TfR, as deletion of CNE1 leads to significant accumulation of the protein. This is the first demonstration of the involvement of CNE1 in regulating the level of heterologous membrane proteins (AU)

Hemos analizado el comportamiento intracelular del receptor de la transferrina humano (TfR) en Saccharomyces cerevisiae. La mayor parte del TfR expresado heterólogamente, usado previamente como modelo de expresión heteróloga de proteínas de membrana en levaduras, se localiza en las membranas del retículo endoplásmico (RE); una fracción menor se encuentra en la membrana plasmática. La estabilidad del TfR depende de proteasas vacuolares, lo cual implica que es degradado en el compartimento vacuolar. La degradación depende asimismo de condiciones favorables de transporte a este compartimento. El factor limitante del transporte parece ser la transición desde el RE a la membrana plasmática. La chaperona Cne1p, implicada en el control de calidad en el RE, juega un papel importante en la regulación de los niveles de TfR heterólogo, ya que la deleción de CNE1 provoca una acumulación significativa de la proteína. Se trata de la primera demostración de la implicación de CNE1 en la regulación de los niveles de proteínas de membrana heterólogas (AU)