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A Conserved Motif Controls Nuclear Localization of Drosophila Muscleblind
Fernandez-Costa, Juan M.,Artero, Ruben Korean Society for Molecular and Cellular Biology 2010 Molecules and cells Vol.30 No.1
Human Muscleblind-like proteins are alternative splicing regulators that are functionally altered in the RNA-mediated disease myotonic dystrophy. There are different Muscleblind protein isoforms in Drosophila and we previously determined that these have different subcellular localizations in the COS-M6 cell line. Here, we describe the conservation of the sequence motif KRAEK in isoforms C and E and propose a specific function for this motif. Different Muscleblind isoforms localize to the peri-plasma membrane (MblA), cytoplasm (MblB), or show no preference for the nuclear or cytoplasmic compartment (MblC and MblD) in Drosophila S2 cells transiently transfected with Musclebind expression plasmids. Mutation of the KRAEK motif reduces MblC nuclear localization, whereas fusion of a single KRAEK motif to the heterologous protein ${\beta}$-galactosidase is sufficient to target the reporter protein to the nucleus of S2 cells. This motif is not exclusive to Muscleblind proteins and is detected in several other protein types. Taken together, these results suggest that the KRAEK motif regulates nuclear translocation of Muscleblind and may constitute a new class of nuclear localization signal.
A Conserved Motif Controls Nuclear Localization of Drosophila Muscleblind
Juan M. Fernandez-Costa,Ruben Artero 한국분자세포생물학회 2010 Molecules and cells Vol.30 No.1
Human Muscleblind-like proteins are alternative splicing regulators that are functionally altered in the RNA-mediated disease myotonic dystrophy. There are different Muscleblind protein isoforms in Drosophila and we previously determined that these have different subcellular localizations in the COS-M6 cell line. Here, we describe the conservation of the sequence motif KRAEK in isoforms C and E and propose a specific function for this motif. Different Muscleblind isoforms localize to the peri-plasma membrane (MblA), cytoplasm (MblB), or show no preference for the nuclear or cytoplasmic compartment (MblC and MblD)in Drosophila S2 cells transiently transfected with Musclebind expression plasmids. Mutation of the KRAEK motif reduces MblC nuclear localization, whereas fusion of a single KRAEK motif to the heterologous protein β-galactosidase is sufficient to target the reporter protein to the nucleus of S2 cells. This motif is not exclusive to Muscleblind proteins and is detected in several other protein types. Taken together, these results suggest that the KRAEK motif regulates nuclear translocation of Muscleblind and may constitute a new class of nuclear localization signal.
Fernandez-Ayala, Daniel J.M.,Sanz, Alberto,Vartiainen, Suvi,Kemppainen, Kia K.,Babusiak, Marek,Mustalahti, Eero,Costa, Rodolfo,Tuomela, Tea,Zeviani, Massimo,Chung, Jongkyeong,O'Dell, Kevin M.C.,Rustin Elsevier 2009 Cell metabolism Vol.9 No.5
<P><B>Summary</B></P><P>Defects in mitochondrial OXPHOS are associated with diverse and mostly intractable human disorders. The single-subunit alternative oxidase (AOX) found in many eukaryotes, but not in arthropods or vertebrates, offers a potential bypass of the OXPHOS cytochrome chain under conditions of pathological OXPHOS inhibition. We have engineered <I>Ciona intestinalis</I> AOX for conditional expression in <I>Drosophila melanogaster.</I> Ubiquitous AOX expression produced no detrimental phenotype in wild-type flies. However, mitochondrial suspensions from AOX-expressing flies exhibited a significant cyanide-resistant substrate oxidation, and the flies were partially resistant to both cyanide and antimycin. AOX expression was able to complement the semilethality of partial knockdown of both <I>cyclope</I> (COXVIc) and the complex IV assembly factor <I>Surf1</I>. It also rescued the locomotor defect and excess mitochondrial ROS production of flies mutated in <I>dj-1</I>β, a <I>Drosophila</I> homolog of the human Parkinson's disease gene <I>DJ1</I>. AOX appears to offer promise as a wide-spectrum therapeutic tool in OXPHOS disorders.</P>
Endoscopic ultrasound-guided gastroenterostomy (gastroenteric anastomosis)
Joel Fernandez de Oliveira,Matheus Cavalcante Franco,Gustavo Rodela,Fauze Maluf-Filho,Bruno Costa Martins 소화기인터벤션의학회 2022 International journal of gastrointestinal interven Vol.11 No.3
Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) has emerged as a promising minimally invasive technique for patients with gastric outlet obstruction (GOO), regardless of whether a benign or malignant condition impedes gastric emptying. EUS-GE involves creating a bypass from the stomach to the small bowel distally to the obstruction, which is similar to the surgical gastroenteric anastomosis. In fact, EUS-GE has been reported to have longer stent patency in patients with malignant GOO than conventional self-expandable metal stents deployed across a malignant obstruction. Although surgical treatment is still considered the gold-standard treatment for patients with malignant GOO, the results of recent studies have shown not only similar rates of technical and clinical success with EUS-GE, but also lower rates of adverse events. In this review, we aimed to appraise the current status of EUS-GE, describe the multiple techniques to perform this procedure, compare the outcomes of EUS-GE with those of other therapeutic modalities, and discuss the related adverse events and the future perspectives of EUS-GE.
Endoscopic ultrasound-guided gastroenterostomy (gastroenteric anastomosis)
Joel Fernandez de Oliveira,Matheus Cavalcante Franco,Gustavo Rodela,Fauze Maluf-Filho,Bruno Costa Martins 소화기인터벤션의학회 2022 Gastrointestinal Intervention Vol.11 No.3
Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) has emerged as a promising minimally invasive technique for patients with gastric outlet obstruction (GOO), regardless of whether a benign or malignant condition impedes gastric emptying. EUS-GE involves creating a bypass from the stomach to the small bowel distally to the obstruction, which is similar to the surgical gastroenteric anastomosis. In fact, EUS-GE has been reported to have longer stent patency in patients with malignant GOO than conventional self-expandable metal stents deployed across a malignant obstruction. Although surgical treatment is still considered the gold-standard treatment for patients with malignant GOO, the results of recent studies have shown not only similar rates of technical and clinical success with EUS-GE, but also lower rates of adverse events. In this review, we aimed to appraise the current status of EUS-GE, describe the multiple techniques to perform this procedure, compare the outcomes of EUS-GE with those of other therapeutic modalities, and discuss the related adverse events and the future perspectives of EUS-GE.