ALS-linked protein disulfide isomerase variants cause motor dysfunction

Simple item page
dc.contributor.authorWoehlbier, Ute
dc.contributor.authorColombo, Alicia
dc.contributor.authorSaaranen, Mirva
dc.contributor.authorPérez, Viviana
dc.contributor.authorOjeda, Jorge
dc.contributor.authorBustos, Fernando
dc.contributor.authorAndreu, Catherine
dc.contributor.authorTorres, mauricio
dc.contributor.authorValenzuela, Vicente
dc.contributor.authorMedinas, Danilo
dc.contributor.authorRozas, Pablo
dc.contributor.authorVidal, René
dc.contributor.authorLópez-González, Rodrigo
dc.contributor.authorSalameh, Johnny
dc.contributor.authorFernández-Collemann, Sara
dc.contributor.authorMuñoz, Natalia
dc.contributor.authorMatus, Soledad
dc.contributor.authorArmisén, Ricardo
dc.contributor.authorSagredo, Alfredo
dc.contributor.authorPalma, Karina
dc.contributor.authorIrrazabal, Thergiory
dc.contributor.authorAlmeida, Sandra
dc.contributor.authorGonzález-Pérez, Paloma
dc.contributor.authorCampero, Mario
dc.date.accessioned2017-01-04T18:05:47Z
dc.date.available2017-01-04T18:05:47Z
dc.date.issued2016
dc.description.abstractDisturbance of endoplasmic reticulum (ER) proteostasis is a common feature of amyotrophic lateral sclerosis (ALS). Protein disulfide isomerases (PDIs) areERfoldases identified as possibleALSbiomarkers, as well as neuroprotective factors. However, no functional studies have addressed their impact on the disease process. Here, we functionally characterized fourALS-linked mutations recently identified in two majorPDIgenes,PDIA1 andPDIA3/ERp57. Phenotypic screening in zebrafish revealed that the expression of thesePDIvariants induce motor defects associated with a disruption of motoneuron connectivity. Similarly, the expression of mutantPDIs impaired dendritic outgrowth in motoneuron cell culture models. Cellular and biochemical studies identified distinct molecular defects underlying the pathogenicity of thesePDImutants. Finally, targetingERp57 in the nervous system led to severe motor dysfunction in mice associated with a loss of neuromuscular synapses. This study identifiesERproteostasis imbalance as a risk factor forALS, driving initial stages of the disease.
dc.identifier.citationWoehlbier U, Colombo A, Saaranen MJ, Pérez V, Ojeda J, Bustos FJ, Andreu CI, Torres M, Valenzuela V, Medinas DB, Rozas P, Vidal RL, Lopez-Gonzalez R, Salameh J, Fernandez-Collemann S, Muñoz N, Matus S, Armisen R, Sagredo A, Palma K, Irrazabal T, Almeida S, Gonzalez-Perez P, Campero M, Gao FB, Henny P, van Zundert B, Ruddock LW, Concha ML, Henriquez JP, Brown RH, Hetz C. ALS-linked protein disulfide isomerase variants cause motor dysfunction. EMBO J. 2016 Apr 15;35(8):845-65.
dc.identifier.urihttp://hdl.handle.net/11447/925
dc.identifier.urihttp://dx.doi.org/ 10.15252/embj.201592224
dc.language.isoen_US
dc.publisherEuropean Molecular Biology Organization by IRL Press
dc.subjectERp57
dc.subjectPDIA1
dc.subjectAmyotrophic lateral sclerosis
dc.subjectProtein disulfide isomerase
dc.titleALS-linked protein disulfide isomerase variants cause motor dysfunction
dc.typeArtículo

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
ALS-linked protein disulfide isomerase variants cause motor dysfunction.pdf
Size:
2.52 MB
Format:
Adobe Portable Document Format
Description:
Texto completo
Download

Collections

Artículos Medicina y Ciencias de la Salud

Implementado por OpenGeek Services