Abstract
The endoplasmic reticulum (ER) is an organelle in which secretory and transmembrane proteins are folded or processed, and is susceptible to various stresses that provoke the accumulation of unfolded proteins in the ER lumen. Recently, ER stress has been reported to be linked to neuronal death in various neurodegenerative diseases. Neurons contain the ER not only in the soma, but also in the dendrites, thus presenting a different case to non-neuronal cells. The ER in the dendrites has potential functions in local protein synthesis and sorting of synthesized proteins to postsynaptic membranes. It raises the possibility that ER stress could occur locally in the dendrites. Here we showed that ER stress sensors, inositol-requiring 1 (IRE1), PKR-like endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6) exist in the ER of both soma and dendrites in primary mouse neurons, and that under ER stress conditions, GRP78/BiP and phosphorylated eIF2alpha are induced. Furthermore, XBP1 mRNA was localized in the proximal dendrites where IRE1 was rapidly phosphorylated in response to ER stress. These results indicate that the ER in dendrites could respond to ER stress and retain the capacity of protein quality control.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Activating Transcription Factor 6 / metabolism
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Animals
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Cells, Cultured
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DNA-Binding Proteins / metabolism
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Dendrites / drug effects
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Dendrites / ultrastructure*
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Embryo, Mammalian
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Endoplasmic Reticulum / drug effects
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Endoplasmic Reticulum / metabolism*
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Endoplasmic Reticulum Chaperone BiP
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Endoribonucleases / metabolism
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology
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Green Fluorescent Proteins / biosynthesis
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Hippocampus / cytology*
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In Situ Hybridization / methods
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Mice
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Nerve Tissue Proteins / metabolism
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Neurons / drug effects
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Neurons / ultrastructure*
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Nuclear Proteins / metabolism
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Phosphorylation / drug effects
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Protein Serine-Threonine Kinases / metabolism
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Regulatory Factor X Transcription Factors
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Stress, Physiological / chemically induced
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Stress, Physiological / metabolism*
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Time Factors
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Transcription Factors
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Transfection / methods
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Tunicamycin / pharmacology
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X-Box Binding Protein 1
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eIF-2 Kinase / metabolism
Substances
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Activating Transcription Factor 6
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Atf6 protein, mouse
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DNA-Binding Proteins
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Endoplasmic Reticulum Chaperone BiP
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Hspa5 protein, mouse
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Nerve Tissue Proteins
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Nuclear Proteins
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Regulatory Factor X Transcription Factors
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Transcription Factors
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X-Box Binding Protein 1
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Xbp1 protein, mouse
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Tunicamycin
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Green Fluorescent Proteins
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Ern1 protein, mouse
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PERK kinase
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Protein Serine-Threonine Kinases
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eIF-2 Kinase
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Endoribonucleases