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Endoplasmic reticulum (ER) remodeling is vital for cellular organization. ER-phagy, a selective autophagy targeting ER, plays an important role in maintaining ER morphology and function. The FAM134 protein family, including FAM134A, FAM134B, and FAM134C, mediates ER-phagy.
View Article and Find Full Text PDFCSNK2/CK2 regulates selective autophagy of the endoplasmic reticulum.
Autophagy
July 2024
Institute of Biochemistry II (IBC2), Faculty of Medicine, Goethe University, Frankfurt am Main, Germany.
Tuning and assimilation of endoplasmic reticulum (ER) content in each cell of the human body is an essential part of organismal homeostasis and adaptation to stress. As such, the lysosomal turnover of ER (reticulophagy) needs to be regulated in a spatio-temporal as well as cell-type specific manner. We recently identified CSNK2/CK2 (casein kinase 2) as the enzyme that phosphorylates the reticulophagy receptors RETREG1/FAM134B and RETREG3/FAM134C and regulates their activity.
View Article and Find Full Text PDFThe function of ER-phagy receptors is regulated through phosphorylation-dependent ubiquitination pathways.
Nat Commun
December 2023
Institute of Biochemistry II (IBC2), Faculty of Medicine, Goethe University, Frankfurt am Main, Germany.
Selective autophagy of the endoplasmic reticulum (ER), known as ER-phagy, is an important regulator of ER remodeling and essential to maintain cellular homeostasis during environmental changes. We recently showed that members of the FAM134 family play a critical role during stress-induced ER-phagy. However, the mechanisms on how they are activated remain largely unknown.
View Article and Find Full Text PDFMolecular characterization of wild-type and HSAN2B-linked FAM134B.
Mol Biol Rep
July 2023
Graduate School of Natural Science and Technology, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan.
Background: Family with sequence similarity 134, member B (FAM134B), also known as Reticulophagy regulator 1 (RETREG1), is an ER-phagy receptor involved in ER homeostasis. Congenital mutations in the FAM134B gene have been reported to be associated with hereditary sensory and autonomic neuropathy type 2B (HSAN2B); however, the molecular differences between wild-type and HSAN2B-linked FAM134B are not fully understood.
Methods And Results: We prepared several human FAM134B constructs, such as the HSAN2B-linked mutant, and compared their features with those of wild-type FAM134B by transfecting these constructs into FAM134B-deficient Neuro2a cells.
Heteromeric clusters of ubiquitinated ER-shaping proteins drive ER-phagy.
Nature
June 2023
Institute of Human Genetics, Jena University Hospital, Friedrich Schiller University, Jena, Germany.
Membrane-shaping proteins characterized by reticulon homology domains play an important part in the dynamic remodelling of the endoplasmic reticulum (ER). An example of such a protein is FAM134B, which can bind LC3 proteins and mediate the degradation of ER sheets through selective autophagy (ER-phagy). Mutations in FAM134B result in a neurodegenerative disorder in humans that mainly affects sensory and autonomic neurons.
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