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PDBsum entry 4zdv
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Protein transport
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PDB id
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4zdv
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References listed in PDB file
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Key reference
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Title
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Regulation of endoplasmic reticulum turnover by selective autophagy.
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Authors
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A.Khaminets,
T.Heinrich,
M.Mari,
P.Grumati,
A.K.Huebner,
M.Akutsu,
L.Liebmann,
A.Stolz,
S.Nietzsche,
N.Koch,
M.Mauthe,
I.Katona,
B.Qualmann,
J.Weis,
F.Reggiori,
I.Kurth,
C.A.Hübner,
I.Dikic.
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Ref.
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Nature, 2015,
522,
354-358.
[DOI no: ]
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PubMed id
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Abstract
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The endoplasmic reticulum (ER) is the largest intracellular endomembrane system,
enabling protein and lipid synthesis, ion homeostasis, quality control of newly
synthesized proteins and organelle communication. Constant ER turnover and
modulation is needed to meet different cellular requirements and autophagy has
an important role in this process. However, its underlying regulatory mechanisms
remain unexplained. Here we show that members of the FAM134 reticulon protein
family are ER-resident receptors that bind to autophagy modifiers LC3 and
GABARAP, and facilitate ER degradation by autophagy ('ER-phagy'). Downregulation
of FAM134B protein in human cells causes an expansion of the ER, while FAM134B
overexpression results in ER fragmentation and lysosomal degradation. Mutant
FAM134B proteins that cause sensory neuropathy in humans are unable to act as
ER-phagy receptors. Consistently, disruption of Fam134b in mice causes expansion
of the ER, inhibits ER turnover, sensitizes cells to stress-induced apoptotic
cell death and leads to degeneration of sensory neurons. Therefore, selective
ER-phagy via FAM134 proteins is indispensable for mammalian cell homeostasis and
controls ER morphology and turnover in mice and humans.
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