Critical roles of FAM134B in ER-phagy and diseases

Mo, Jie; Jin, Cheqing; Zhang, Bixiang

doi:10.1038/s41419-020-03195-1

Cited by 39 publications

(29 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While there is a growing body of literature on the physiological and pathological roles of FAM134B (Mo et al , 2020 ), FAM134A and FAM134C are still poorly studied. FAM134A has been associated with mitotic progression (Toyoda et al , 2017 ) and is a target of hsa‐miRNA940 in the regulation of osteogenic differentiation (Hashimoto et al , 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Role of FAM134 paralogues in endoplasmic reticulum remodeling, ER‐phagy, and Collagen quality control

et al. 2021

View full text Add to dashboard Cite

Degradation of the endoplasmic reticulum (ER) via selective autophagy (ER‐phagy) is vital for cellular homeostasis. We identify FAM134A/RETREG2 and FAM134C/RETREG3 as ER‐phagy receptors, which predominantly exist in an inactive state under basal conditions. Upon autophagy induction and ER stress signal, they can induce significant ER fragmentation and subsequent lysosomal degradation. FAM134A, FAM134B/RETREG1, and FAM134C are essential for maintaining ER morphology in a LC3‐interacting region (LIR)‐dependent manner. Overexpression of any FAM134 paralogue has the capacity to significantly augment the general ER‐phagy flux upon starvation or ER‐stress. Global proteomic analysis of FAM134 overexpressing and knockout cell lines reveals several protein clusters that are distinctly regulated by each of the FAM134 paralogues as well as a cluster of commonly regulated ER‐resident proteins. Utilizing pro‐Collagen I, as a shared ER‐phagy substrate, we observe that FAM134A acts in a LIR‐independent manner and compensates for the loss of FAM134B and FAM134C, respectively. FAM134C instead is unable to compensate for the loss of its paralogues. Taken together, our data show that FAM134 paralogues contribute to common and unique ER‐phagy pathways.

show abstract

Section: Discussionmentioning

confidence: 99%

Role of FAM134 paralogues in endoplasmic reticulum remodeling, ER‐phagy, and Collagen quality control

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The protein has been reported to localize to the ER membrane, specifically to tubules and sheet edges (Khaminets et al, 2015;Mo et al, 2020), and in another study, the protein has been shown to primarily localize to the Golgi apparatus (Kurth et al, 2009). The RHD of FAM134B is required for membrane fragmentation in vitro and ER-phagy in vivo under ER stress (Bhaskara et al, 2019;Jiang et al, 2020;D'Eletto et al, 2020).…”

Section: Introductionmentioning

confidence: 94%

“…The protein has been reported to localize to the ER membrane, specifically to tubules and sheet edges ( Khaminets et al. , 2015 ; Mo et al. , 2020 ), and in another study, the protein has been shown to primarily localize to the Golgi apparatus ( Kurth et al.…”

Section: Introductionmentioning

confidence: 97%

RTN4B interacting protein FAM134C promotes ER membrane curvature and has a functional role in autophagy

Kumar

Lak

Suntio

et al. 2021

MBoC

View full text Add to dashboard Cite

The endoplasmic reticulum (ER) is comprised of a controlled ratio of sheets and tubules, which are maintained by several proteins with multiple functions. Reticulons (RTNs), especially RTN4, and DP1/Yop1p family members are known to induce ER membrane curvature. RTN4B is the main RTN4 isoform expressed in non-neuronal cells. In this study, we identified FAM134C as a RTN4B interacting protein in mammalian, non-neuronal cells. FAM134C localized specifically to the ER tubules and sheet edges. Ultrastructural analysis revealed that overexpression of FAM134C induced formation of unbranched, long tubules or dense globular structures comprised of heavily branched narrow tubules. In both cases, tubules were non-motile. ER tubulation was dependent on the reticulon homology domain (RHD) close to the N-terminus. FAM134C plays a role in the autophagy pathway as its level elevated significantly upon amino acid starvation but not during ER stress. Moreover, FAM134C depletion reduced the number and size of autophagic structures and the amount of ER as a cargo within autophagic structures under starvation conditions. Dominant-negative expression of FAM134C forms with mutated RHD or LC3 interacting region (LIR) also led to the reduced number of autophagic structures. Our results suggest that FAM134C provides a link between regulation of ER architecture and ER turnover by promoting ER tubulation required for subsequent ER fragmentation and engulfment into autophagosomes. [Media: see text] [Media: see text] [Media: see text] [Media: see text]

show abstract

“…Accordingly, they cannot bind LC3/GABARAP family members or mediate ER-phagy. In this case, impaired ER-phagy flux may contribute to the pathogenesis of HSAN II [ 85 , 86 , 87 , 88 ]. However, other mutations identified from HSAN II patients, such as c.646 G > A (p.G216R), may make FAM134B overactive, thus inducing excessive ER-phagy.…”

Section: The Diseases Relevance Of Er-phagymentioning

confidence: 99%

Advances in ER-Phagy and Its Diseases Relevance

Qian

Cui

2021

Cells

View full text Add to dashboard Cite

As an important form of selective autophagy in cells, ER-phagy (endoplasmic reticulum-selective autophagy), the autophagic degradation of endoplasmic reticulum (ER), degrades ER membranes and proteins to maintain cellular homeostasis. The relationship between ER-phagy and human diseases, including neurodegenerative disorders, cancer, and other metabolic diseases has been unveiled by extensive research in recent years. Starting with the catabolic process of ER-phagy and key mediators in this pathway, this paper reviews the advances in the mechanism of ER-phagy and its diseases relevance. We hope to provide some enlightenment for further study on ER-phagy and the development of novel therapeutic strategies for related diseases.

show abstract

Critical roles of FAM134B in ER-phagy and diseases

Cited by 39 publications

References 93 publications

Role of FAM134 paralogues in endoplasmic reticulum remodeling, ER‐phagy, and Collagen quality control

Role of FAM134 paralogues in endoplasmic reticulum remodeling, ER‐phagy, and Collagen quality control

RTN4B interacting protein FAM134C promotes ER membrane curvature and has a functional role in autophagy

Advances in ER-Phagy and Its Diseases Relevance

Contact Info

Product

Resources

About