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Autophagic degradation of stromal interaction molecule 2 mediates disruption of neuronal dendrites by endoplasmic reticulum stress
Author(s) -
Zhou Jing,
Song Juan,
Wu Shengzhou
Publication year - 2019
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14712
Subject(s) - endoplasmic reticulum , microbiology and biotechnology , unfolded protein response , autophagy , dendrite (mathematics) , neurodegeneration , tunicamycin , chemistry , biology , neuroscience , medicine , apoptosis , biochemistry , geometry , mathematics , disease
Endoplasmic reticulum ( ER ) stress has been highlighted as one of the factors involved in axon/dendrite degeneration, which is an early event in Alzheimer's, Parkinson's diseases as well as in acute disorders such as ischemia and axotomy‐induced retinal ganglion cell degeneration. These lines of evidence suggest critical roles of ER stress at the early stage of neurodegeneration, but the relevant mechanism is rarely exploited. In this study, we report that treatment with sublethal level of ER stressors, tunicamycin or brefeldin A, in primary rat neuronal cultures, significantly reduced dendrite arbor. Under the same treatment, either stressor reduced store‐operated calcium entry ( SOCE ) and cytosolic calcium, [Ca 2+ ] i , which were associated with autophagic degradation of stromal interaction molecule 2 ( STIM 2). Knockdown of ATG 7 or activating transcription factor 4 completely reversed the reduction of STIM 2 and significantly reversed the inhibition of SOCE under ER stress. Overexpression of STIM 2 in neurons significantly prevented the ER stress‐induced disruption of dendrite arbor. Altogether, our data reveal an unprecedented mechanism by which ER stress induces dendrite degeneration, that is, ER stress induces autophagic degradation of STIM 2, leading to ensued SOCE inhibition and reduced [Ca 2+ ] i , resulting in trimming effect on dendrites.