RESUMEN
Neuronal endoplasmic reticulum (ER) appears continuous throughout the cell. Its shape and continuity are influenced by ER-shaping proteins, mutations in which can cause distal axon degeneration in Hereditary Spastic Paraplegia (HSP). We therefore asked how loss of Rtnl1, a Drosophila ortholog of the human HSP gene RTN2 (SPG12), which encodes an ER-shaping protein, affects ER organization and the function of presynaptic terminals. Loss of Rtnl1 depleted ER membrane markers at Drosophila presynaptic motor terminals and appeared to deplete narrow tubular ER while leaving cisternae largely unaffected, thus suggesting little change in resting Ca2+ storage capacity. Nevertheless, these changes were accompanied by major reductions in activity-evoked Ca2+ fluxes in the cytosol, ER lumen, and mitochondria, as well as reduced evoked and spontaneous neurotransmission. We found that reduced STIM-mediated ER-plasma membrane contacts underlie presynaptic Ca2+ defects in Rtnl1 mutants. Our results show the importance of ER architecture in presynaptic physiology and function, which are therefore potential factors in the pathology of HSP.
Asunto(s)
Calcio , Proteínas de Drosophila , Drosophila , Retículo Endoplásmico , Proteínas de la Membrana , Animales , Humanos , Calcio/metabolismo , Proteínas de Drosophila/genética , Retículo Endoplásmico/metabolismo , Proteínas de la Membrana/genética , Paraplejía Espástica Hereditaria/genética , Paraplejía Espástica Hereditaria/patologíaRESUMEN
[This corrects the article DOI: 10.3389/fcell.2021.749723.].
RESUMEN
Muscle development is a multistep process that involves cell specification, myoblast fusion, myotube migration, and attachment to the tendons. In spite of great efforts trying to understand the basis of these events, little is known about the molecular mechanisms underlying myotube migration. Knowledge of the few molecular cues that guide this migration comes mainly from studies in Drosophila. The migratory process of Drosophila embryonic muscles involves a first phase of migration, where muscle progenitors migrate relative to each other, and a second phase, where myotubes migrate searching for their future attachment sites. During this phase, myotubes form extensive filopodia at their ends oriented preferentially toward their attachment sites. This myotube migration and the subsequent muscle attachment establishment are regulated by cell adhesion receptors, such as the conserved proteoglycan Kon-tiki/Perdido. Laminins have been shown to regulate the migratory behavior of many cell populations, but their role in myotube migration remains largely unexplored. Here, we show that laminins, previously implicated in muscle attachment, are indeed required for muscle migration to tendon cells. Furthermore, we find that laminins genetically interact with kon-tiki/perdido to control both myotube migration and attachment. All together, our results uncover a new role for the interaction between laminins and Kon-tiki/Perdido during Drosophila myogenesis. The identification of new players and molecular interactions underlying myotube migration broadens our understanding of muscle development and disease.
RESUMEN
The physical continuity of axons over long cellular distances poses challenges for their maintenance. One organelle that faces this challenge is endoplasmic reticulum (ER); unlike other intracellular organelles, this forms a physically continuous network throughout the cell, with a single membrane and a single lumen. In axons, ER is mainly smooth, forming a tubular network with occasional sheets or cisternae and low amounts of rough ER. It has many potential roles: lipid biosynthesis, glucose homeostasis, a Ca2+ store, protein export, and contacting and regulating other organelles. This tubular network structure is determined by ER-shaping proteins, mutations in some of which are causative for neurodegenerative disorders such as hereditary spastic paraplegia (HSP). While axonal ER shares many features with the tubular ER network in other contexts, these features must be adapted to the long and narrow dimensions of axons. ER appears to be physically continuous throughout axons, over distances that are enormous on a subcellular scale. It is therefore a potential channel for long-distance or regional communication within neurons, independent of action potentials or physical transport of cargos, but involving its physiological roles such as Ca2+ or organelle homeostasis. Despite its apparent stability, axonal ER is highly dynamic, showing features like anterograde and retrograde transport, potentially reflecting continuous fusion and breakage of the network. Here we discuss the transport processes that must contribute to this dynamic behavior of ER. We also discuss the model that these processes underpin a homeostatic process that ensures both enough ER to maintain continuity of the network and repair breaks in it, but not too much ER that might disrupt local cellular physiology. Finally, we discuss how failure of ER organization in axons could lead to axon degenerative diseases, and how a requirement for ER continuity could make distal axons most susceptible to degeneration in conditions that disrupt ER continuity.
RESUMEN
Genes for endoplasmic reticulum (ER)-shaping proteins are among the most commonly mutated in hereditary spastic paraplegia (HSP). Mutation of these genes in model organisms can lead to disruption of the ER network. To investigate how the physiological roles of the ER might be affected by such disruption, we developed tools to interrogate its Ca2+ signaling function. We generated GAL4-driven Ca2+ sensors targeted to the ER lumen, to record ER Ca2+ fluxes in identified Drosophila neurons. Using GAL4 lines specific for Type Ib or Type Is larval motor neurons, we compared the responses of different lumenal indicators to electrical stimulation, in axons and presynaptic terminals. The most effective sensor, ER-GCaMP6-210, had a Ca2+ affinity close to the expected ER lumenal concentration. Repetitive nerve stimulation generally showed a transient increase of lumenal Ca2+ in both the axon and presynaptic terminals. Mutants lacking neuronal reticulon and REEP proteins, homologs of human HSP proteins, showed a larger ER lumenal evoked response compared to wild type; we propose mechanisms by which this phenotype could lead to neuronal dysfunction or degeneration. Our lines are useful additions to a Drosophila Ca2+ imaging toolkit, to explore the physiological roles of ER, and its pathophysiological roles in HSP and in axon degeneration more broadly.
RESUMEN
En relación a los sistemas de memoria de nuestra investigación, clasificamos la memoria explícita, voluntaria, consciente; mientras que la memoria implícita no requiere la recuperación intencional o consciente. Además del envejecimiento, las enfermedades psiquiátricas constituyen otras causas frecuentes de deterioro cognitivo; más específicamente, en el Trastorno psicótico están afectadas la memoria declarativa verbal (explícita), la memoria de trabajo y existen otros déficits cognitivos. Metodología: El objetivo de este estudio consiste en analizar la evolución del Trastorno psicótico (en años) en relación a la memoria y al deterioro cognitivo, así como describir posibles asociaciones entre ambos tipos de memoria (implícita/explícita) y el deterioro cognitivo. Se trata de un estudio descriptivo, observacional, transversal, formado por tres muestras de pacientes con Trastorno psicótico. Resultados: Se obtienen proporciones medias mayores en los dos primeros grupos (0-5 años de evolución del Trastorno psicótico/ 10-15 años de evolución) que en el tercer grupo (25-35 años de evolución) para los resultados de memoria explícita. Respecto a la memoria implícita se observa la existencia de Priming en los tres grupos. Mientras que la puntuación positiva en el cribado de deterioro cognitivo es progresivamente mayor al aumentar los años de evolución de la enfermedad. Conclusiones: Las personas con más años de evolución del trastorno psicótico presentan mayor deterioro cognitivo y puntuaciones medias menores en memoria explícita; mientras que la memoria implícita se mantiene estable independientemente de los años de evolución de la enfermedad (AU)
In relation to systems of memory of our research report, we classify the memory explicit, voluntary, conscious; While the implicit memory does not require deliberate or conscious recovery. In addition to aging, psychiatric diseases are other common causes of cognitive impairment; more specifically, the psychotic disorder affected the declarative (explicit) verbal memory, working memory and there are other cognitive deficits. Methodology: The objective of this study is to analyze the evolution of the psychotic disorder (in years) in relation to memory and cognitive impairment, as well as describe possible associations between the two types of cognitive impairment and memory (implicitaexplicita). It is a descriptive, observational, transversal study consisting of three samples of patients with psychotic disorder. Results: Average proportions in the first two groups (0-5 years of evolution of the psychotic disorder 10 - 15 years of evolution) in the third group (25-35 years of evolution) to the results of explicit memory. Regarding the implicit memory is observed the existence of Priming in the three groups. While scoring positive in the screening of cognitive impairment it is progressively higher by increasing the years of evolution of the disease. Conclusions: People with more years of evolution of the psychotic disorder have greater cognitive impairment and average scores lower in explicit memory; While the implicit memory stays stable regardless of the years of evolution of the disease (AU)
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Trastornos Psicóticos/complicaciones , Memoria , Disfunción Cognitiva/etiología , Índice de Severidad de la Enfermedad , Proyectos Piloto , Estudio Observacional , Estudios Transversales , EspañaRESUMEN
En marzo de 2020 la Organización Mundial de la Salud (OMS) declara la situación de pandemia por COVID-19. En situaciones de crisis como puede ser una pandemia, las personas reaccionan y responden de diversas maneras en el ámbito psicosomático. Existe evidencia de que la Primera Ayuda Psicología (PAP) resulta un apoyo efectivo tras un acontecimiento crítico. En este artículo se expone la experiencia de un equipo de enfermeras especialistas en salud mental en el Servicio de Urgencias del Hospital Galdakao-Usansolo (Bizkaia) durante la pandemia de la COVID-19 en el periodo comprendido entre marzo y mayo del año 2020. El objetivo de este texto es dar a conocer las actuaciones desarrolladas durante esta crisis sanitaria para que pueda servir como modelo de futuros protocolos de actuación que recojan estas acciones o similares, con el fin último de mejorar la calidad de la atención a las familias, pacientes y profesionales (sobre todo desde el plano emocional) en una situación de pandemia y/o aislamiento hospitalario, tanto en el hospital en el que se han llevado a cabo, como en otros centros sanitarios y sociosanitarios, dentro y fuera de la comunidad autónoma vasca
On March, 2020, the World Health Organization (WHO) declared the pandemic situation by COVID-19. In scenarios of crisis such as a pandemic, persons will react and respond in different ways in the psychosomatic setting. There is evidence that Psychological First Aid (PFA) provides effective support after a critical event. This article describes the experience of a team of nurses specialized in mental health from the Emergency Unit of the Hospital Galdakao-Usansolo (Basque Country) during the COVID-19 pandemic in the period between March and May, 2020. The objective of this article is to make public the actions conducted during this health crisis, in order to become the model for future protocols of action collecting these or similar actions, with the ultimate goal to improve care for families, patients and professionals (particularly at emotional level) in a scenario of pandemic and/or hospital isolation, in the hospital where they have been implemented as well as in other healthcare and sociosanitary centers, inside and outside the Basque Autonomous Community