ABSTRACT
Neurotransmitter transporter ubiquitination is emerging as the main mechanism for endocytosis and sorting of cargo into lysosomes. In this study, we demonstrate PKC-dependent ubiquitination of three different isoforms of the glycine transporter 1 (GlyT1). Incubation of cells expressing transporter with the PKC activator phorbol ester induced a dramatic, time-dependent increase in GlyT1 ubiquitination, followed by accumulation of GlyT1 in EEA1 positive early endosomes. This occurred via a mechanism that was abolished by inhibition of PKC. GlyT1 endocytosis was confirmed in both retinal sections and primary cultures of mouse amacrine neurons. Replacement of only all lysines in the N-and C-termini to arginines prevented ubiquitination and endocytosis, displaying redundancy in the mechanism of ubiquitination. Interestingly, a 40-50% reduction in glycine uptake was detected in phorbol-ester stimulated cells expressing the WT-GlyT1, whereas no significant change was for the mutant protein, demonstrating that endocytosis participates in the reduction of uptake. Consistent with previous findings for the dopamine transporter DAT, ubiquitination of GlyT1 tails functions as sorting signal to deliver transporter into the lysosome and removal of ubiquitination sites dramatically attenuated the rate of GlyT1 degradation. Finally, we showed for the first time that PKC-dependent GlyT1 phosphorylation was not affected by removal of ubiquitination sites, suggesting separate PKC-dependent signaling events for these posttranslational modifications.
Subject(s)
Endocytosis/physiology , Glycine Plasma Membrane Transport Proteins/metabolism , Neurons/metabolism , Protein Kinase C/antagonists & inhibitors , Animals , Dopamine Plasma Membrane Transport Proteins/metabolism , Mice , Mice, Inbred C57BL , Phorbol Esters/pharmacology , Phosphorylation , Protein Kinase C/metabolism , Signal Transduction , Swine , UbiquitinationABSTRACT
Se efectuó un estudio descriptivo retrospectivo, con el objetivo de identificar los principales hábitos bucales deformantes y las maloclusiones asociadas a los mismos, que presentaron los pacientes ingresados en el servicio de ortodoncia de la Clínica Estomatológica Docente Provincial 3 de Octubre de la provincia de Las Tunas, en el período comprendido entre enero y diciembre de 2012. El universo estuvo constituido por 235 historias clínicas de los pacientes ingresados en el servicio en el período de estudio, que fueron revisadas y se seleccionó una muestra de 91 pacientes según criterios establecidos. Dentro de los principales resultados, los hábitos de respiración bucal y la deglución atípica fueron los más comunes y la disfunción neuromuscular con mayor incidencia fue la del orbicular de los labios. El sexo más afectado fue el femenino, el grupo de seis a 11 años de edad fue el más representativo y más de la mitad de la muestra presentó Clase I de Angle (AU)
A descriptive and retrospective study was carried out aimed at identifying the main deforming buccal habits and their associated malocclusions in patients admitted to the orthodontics service of 3 de Octubre Provincial Teaching Dental Office in Las Tunas, from January to December, 2012. The universe consisted of the 235 checked health histories of the patients admitted to the service in the period of study, and the sample was made up by 91 patients selected according to the established criteria. Among the main results, the habits of mouth breathing and the atypical swallowing were the most common ones, and the neuromuscular dysfunction with the highest incidence was that of the orbicularis oris. Females were the most affected ones, the 6 to 10 age group was the most representative one, and more than half of the sample presented Angles Class I (AU)
Subject(s)
Humans , Female , Child , Malocclusion, Angle Class I , Mouth Breathing , Epidemiology, Descriptive , Retrospective StudiesABSTRACT
Las alteraciones dentarias se clasifican en anomalías de número, tamaño y forma. Estas anomalías pueden provocar diversos problemas funcionales y estéticos, por ello es necesario un correcto diagnóstico para un tratamiento precoz que involucra generalmente un abordaje multidisciplinario. El objetivo de este artículo es presentar dos casos donde fue diagnosticada la presencia de agenesia dentaria y microdoncia, la corrección ortodóncica y la rehabilitación estética de los mismos (AU)
Dental disorders are classified into number, size and form anomalies. These anomalies can cause several functional and aesthetic problems and therefore it is necessary to make a correct diagnosis for an early treatment that generally involves a multidisciplinary work. The aim of this article is to present two cases diagnosed with dental agenesis and microdontia. It includes the orthodontic correction and the aesthetic rehabilitation (AU)
