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GSK-3?-dependent downregulation of ?-taxilin and ?NAC merge to regulate ER stress responses.

ABSTRACT: The signaling pathway leading to the endoplasmic reticulum (ER) stress responses has not been fully elucidated. Here we showed that glycogen synthase kinase-3? (GSK-3?)-dependent downregulation of ?-taxilin and nascent polypeptide-associated complex ?-subunit (?NAC) mediates hypoxia-induced unfolded protein responses (UPRs) and the subsequent apoptotic and autophagic pathways. The degradation of ?-taxilin or ?NAC was sufficient to initiate UPRs in normoxic cells. However, the ER stress signaling pathways initiated by ?-taxilin or ?NAC were distinct, triggering different ER stress sensors and activating different downstream pathways. Hypoxia caused GSK-3?-dependent tau hyperphosphorylation and cleavage in neuronal cells, but ?-taxilin ablation induced tau hyperphosphorylation alone and ?NAC ablation induced neither changes. Notably, downregulation of ?-taxilin and ?NAC occurs in the brain of patients with Alzheimer's disease. These results suggest that GSK-3?-dependent downregulation of ?-taxilin and ?NAC, which differently activate the UPRs, merge to regulate hypoxia-induced ER stress responses and provide a new insight into the pathogenesis of neurodegenerative diseases.

SUBMITTER: Hotokezaka Y

PROVIDER: S-EPMC4650556 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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GSK-3β-dependent downregulation of γ-taxilin and αNAC merge to regulate ER stress responses.

Hotokezaka Y Y Katayama I I van Leyen K K Nakamura T T

Cell death & disease 20150416

The signaling pathway leading to the endoplasmic reticulum (ER) stress responses has not been fully elucidated. Here we showed that glycogen synthase kinase-3β (GSK-3β)-dependent downregulation of γ-taxilin and nascent polypeptide-associated complex α-subunit (αNAC) mediates hypoxia-induced unfolded protein responses (UPRs) and the subsequent apoptotic and autophagic pathways. The degradation of γ-taxilin or αNAC was sufficient to initiate UPRs in normoxic cells. However, the ER stress signaling ...[more]

PMID: 25880086

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Project description:The NAC transcription factors play important roles in regulating plant growth, development, and senescence, and responding to biotic and abiotic stressors in plants. A novel coding sequence (1,059 bp) was cloned from hexaploid triticale in this study. The putative protein (352 amino acids) encoded by this sequence was over 95% similar to the amino acid sequence of a NAC protein from Aegilops tauschii (XP020161331), and it formed a clade with Ae. tauschii, durum wheat, and barley. The putative protein contained a conserved nature actomyosin (NAM) domain (129 consecutive amino acids) between the 20th and 148th amino acids at the N-terminus and three transcription activation regions at the C-terminus. The novel gene was identified as a triticale NAC gene localized in the nucleus and designated as TwNAC01 (GenBank accession MG736919). The expression levels of TwNAC01 were the highest in roots, followed by leaves and stems when triticale lines were exposed to drought, polyethylene glycol 6,000 (PEG6000), NaCl, cold, methyl jasmonate (MeJA), and abscisic acid (ABA). Transgenic Arabidopsis thaliana overexpressing TwNAC01 had significantly lower leaf water loss rates and longer roots than wild-type (WT) A. thaliana. Virus-induced silencing of the TwNAC01 gene in triticale delayed root development and decreased length of primary root. Under drought stress, leaves of TwNAC01-silenced triticale had higher levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2), but lower relative water content (RWC), net photosynthetic rate, stomatal conductance, intercellular CO2 concentration, and transpiration rate than the leaves of the WT. Gene overexpression and silencing experiments suggested that TwNAC01 improves plant stress tolerance by increasing root length, regulating the water content of plant leaves by reducing MDA and H2O2 content, and adjusting respiration rate. The results suggest that TwNAC01 is a novel NAC transcription factor gene that can be exploited for triticale and cereal improvement.

Dataset Information

GSK-3?-dependent downregulation of ?-taxilin and ?NAC merge to regulate ER stress responses.

Publications

GSK-3β-dependent downregulation of γ-taxilin and αNAC merge to regulate ER stress responses.

Similar Datasets

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