Mesencephalic astrocyte–derived neurotrophic factor is an ER-resident chaperone that protects against reductive stress in the heart
Adrian Arrieta, Erik A. Blackwood, Winston T Stauffer, Michelle Santo Domingo, Alina S. Bilal, Donna J. Thuerauf, Amber N Pentoney, Cathrine Aivati, Anup Sarakki, Shirin Doroudgar, Christopher C. Glembotski
Abstract
, recombinant MANF exhibited chaperone activity that depended on its conserved cysteine residues. Moreover, in cells, MANF bound to a model ER protein exhibiting improper disulfide bond formation during reductive ER stress but did not bind to this protein during nonreductive ER stress. We conclude that MANF is an ER chaperone that enhances protein folding and myocyte viability during reductive ER stress.
Topics & Concepts
Unfolded protein responseEndoplasmic reticulumTunicamycinATF6Cell biologyGene knockdownChaperone (clinical)XBP1ChemistryThapsigarginBiologyBiochemistryMedicineRNA splicingApoptosisPathologyRNAGeneEndoplasmic Reticulum Stress and DiseaseAutophagy in Disease and TherapyHeat shock proteins research