Publication

A selective ER‐phagy exerts procollagen quality control via a Calnexin‐FAM134B complex

Maurizio Molinari
2018
Journal Articles

Abstract

Autophagy is a cytosolic quality control process that recognizessubstrates through receptor-mediated mechanisms. Procollagens,the most abundant gene products in Metazoa, are synthesized inthe endoplasmic reticulum (ER), and a fraction that fails to attainthe native structure is cleared by autophagy. However, how auto-phagy selectively recognizes misfolded procollagens in the ERlumen is still unknown. We performed siRNA interference, CRISPR-Cas9or knockout-mediated gene deletion of candidate autophagyand ER proteins in collagen producing cells. We found that the ER-resident lectin chaperone Calnexin (CANX) and the ER-phagyreceptor FAM134B are required for autophagy-mediated qualitycontrol of endogenous procollagens. Mechanistically, CANX acts asco-receptor that recognizes ER luminal misfolded procollagens andinteracts with the ER-phagy receptor FAM134B. In turn, FAM134Bbinds the autophagosome membrane-associated protein LC3anddelivers a portion of ER containing both CANX and procollagen tothe lysosome for degradation. Thus, a crosstalk between the ERquality control machinery and the autophagy pathway selectivelydisposes of proteasome-resistant misfolded clients from the ER.

Official source

https://infoscience.epfl.ch/entities/publication/0d46b6ba-9d50-429a-828d-87ff97769644

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Maurizio Molinari
2018
Journal Articles

Abstract

Official source

https://infoscience.epfl.ch/entities/publication/0d46b6ba-9d50-429a-828d-87ff97769644

About this result

Related concepts (8)

Gene knockout

Gene knockouts (also known as gene deletion or gene inactivation) are a widely used genetic engineering technique that involves the targeted removal or inactivation of a specific gene within an organism's genome. This can be done through a variety of methods, including homologous recombination, CRISPR-Cas9, and TALENs. One of the main advantages of gene knockouts is that they allow researchers to study the function of a specific gene in vivo, and to understand the role of the gene in normal development and physiology as well as in the pathology of diseases.

CRISPR

CRISPR (ˈkrɪspər) (an acronym for clustered regularly interspaced short palindromic repeats) is a family of DNA sequences found in the genomes of prokaryotic organisms such as bacteria and archaea. These sequences are derived from DNA fragments of bacteriophages that had previously infected the prokaryote. They are used to detect and destroy DNA from similar bacteriophages during subsequent infections. Hence these sequences play a key role in the antiviral (i.e. anti-phage) defense system of prokaryotes and provide a form of acquired immunity.

RNA interference

RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by other names, including co-suppression, post-transcriptional gene silencing (PTGS), and quelling. The detailed study of each of these seemingly different processes elucidated that the identity of these phenomena were all actually RNAi. Andrew Fire and Craig C.

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