“At last in” the physiological roles of the tubular ER network

Lü, Li; Niu, Liling; Hu, Junjie

doi:10.1007/s41048-020-00113-y

Cited by 7 publications

(6 citation statements)

References 116 publications

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“…Of all the members of the ATL family, ATL2/3 are expressed in most cell types ( Lü et al, 2020 ). To investigate whether ATLs regulate autophagy, we used ATL2 and ATL3 single knockout (KO) cells and double KO (DKO) COS-7 cells.…”

Section: Resultsmentioning

confidence: 99%

“…Depletion of ATLs results in the formation of long, unbranched, and less mobile ER tubules ( Hu et al, 2009 ). ATLs regulate multiple ER-related processes, such as calcium homeostasis, lipid metabolism, microtubule dynamics, and membrane trafficking ( Lü et al, 2020 ; Niu et al, 2019 ; Park et al, 2010 ). ATLs have been suggested to function in ERphagy, a process referring to selective engulfment of ER fragments into the autophagosome for degradation ( Chino and Mizushima, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Atlastin 2/3 regulate ER targeting of the ULK1 complex to initiate autophagy

Liu

Zhao

et al. 2021

Journal of Cell Biology

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Dynamic targeting of the ULK1 complex to the ER is crucial for initiating autophagosome formation and for subsequent formation of ER–isolation membrane (IM; autophagosomal precursor) contact during IM expansion. Little is known about how the ULK1 complex, which comprises FIP200, ULK1, ATG13, and ATG101 and does not exist as a constitutively coassembled complex, is recruited and stabilized on the ER. Here, we demonstrate that the ER-localized transmembrane proteins Atlastin 2 and 3 (ATL2/3) contribute to recruitment and stabilization of ULK1 and ATG101 at the FIP200-ATG13–specified autophagosome formation sites on the ER. In ATL2/3 KO cells, formation of FIP200 and ATG13 puncta is unaffected, while targeting of ULK1 and ATG101 is severely impaired. Consequently, IM initiation is compromised and slowed. ATL2/3 directly interact with ULK1 and ATG13 and facilitate the ATG13-mediated recruitment/stabilization of ULK1 and ATG101. ATL2/3 also participate in forming ER–IM tethering complexes. Our study provides insights into the dynamic assembly of the ULK1 complex on the ER for autophagosome formation.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Atlastin 2/3 regulate ER targeting of the ULK1 complex to initiate autophagy

Liu

Zhao

et al. 2021

Journal of Cell Biology

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“…The following reference appears in the Supplemental Information: Amson et al., 2013 ; Azim et al., 2009 ; Baritaki et al., 2009 ; Bhaduri et al., 2020 ; Bhat et al., 2011 ; Brozzi et al., 2009 ; Bulstrode et al., 2017 ; de la Rocha et al., 2014 ; Ehmsen et al., 2013 ; Engel et al., 2020 ; Gao et al., 2021 ; Grimm et al., 2020 ; Gu et al., 2014 ; Hagiwara, 2011 ; Harroch et al., 2002 ; Hou et al., 2016 ; Hoxha et al., 2020 ; Koziol et al., 2007 ; Liu et al., 2013 ; Lü et al., 2020 ; Luxen et al., 2017 ; Mani et al., 2008 ; Miao et al., 2019 ; Polisetty et al., 2012 ; Roy et al., 2020 ; Saito et al., 2007 ; Shi et al., 2017 ; Tao et al., 2020 ; Thompson et al., 2009 ; Wang et al., 2013 , 2015 ; Yamasaki et al., 2001 ; Yu et al., 2020 .…”

Section: Supporting Citationsunclassified

Algorithmic reconstruction of glioblastoma network complexity

Uthamacumaran

Craig

2022

iScience

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“…The Atl3 protein belongs to a conserved family of large, dynamin-related GTPases involved in the formation and maintenance of the endoplasmic reticulum (ER) [ 49 , 50 ]. Atlastins, particularly Atl3, are predominantly enriched in the three-way junctions of the ER network and are involved in the biogenesis and regulation of lipid droplets and sterols [ 49 , 51 ]. Lipid droplets are the primary organelles for the storage of fat in cells to accommodate the excess energy in the form of triglycerides and cholesterols within the membrane phospholipid bilayer [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Short-Term Omega-3 Supplementation Modulates Novel Neurovascular and Fatty Acid Metabolic Proteome Changes in the Retina and Ophthalmic Artery of Mice with Targeted Cyp2c44 Gene Deletion

Perumal

Herfurth

Pfeiffer

et al. 2022

Cells

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Cytochrome P450 (CYP) gene mutations are a common predisposition associated with glaucoma. Although the molecular mechanisms are largely unknown, omega-3 polyunsaturated fatty acids (ω-3 PUFA) and their CYP-derived bioactive mediators play crucial roles in the ocular system. Here, we elucidated the proteome and cell-signalling alterations attributed to the main human CYP2C gene deficiency using a homologous murine model (Cyp2c44−/−), and unravelled the effects of acute ω-3 PUFA supplementation in two ocular vascular beds comprising the retrobulbar ophthalmic artery (OA) and retina (R). Male Cyp2c44−/− mice (KO) and their floxed littermates (WT) were gavaged daily for 7 days with 0.01 mL/g of ω-3 PUFA composed of menhaden fish oil. Another group in respective strains served as vehicle-treated controls. OA and R were isolated at day 8 post-treatment (n = 9/group) and subjected to mass spectrometry (MS)-based proteomics and in silico bioinformatics analyses. Cyp2c44−/− resulted in significant detrimental proteome changes associated with compromised vascular integrity and degeneration in the OA and R, respectively. However, notable changes in the OA after ω-3 PUFA intake were associated with the maintenance of intercellular junctional and endothelial cell functions, as well as activation of the fatty acid metabolic pathway in the KO mice. Conversely, ω-3 PUFA supplementation profoundly influenced the regulation of a large majority of retinal proteins involved in the preservation of neuronal and phototransduction activities in WT mice, namely synaptophysin, phosducin and guanylate cyclase-1, while significantly abrogating degenerative processes in the KO mice via the regulation of, namely, synaptotagmin-1 and beta-crystallin B2. In gist, this study demonstrated that dietary supplementation with ω-3 PUFA for a short period of seven days regulated specific neuro-vasculoprotective mechanisms to preserve the functionality of the OA and R in the absence of Cyp2c44. The potential adjunct use of ω-3 PUFA for glaucoma therapy needs further investigation.

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“At last in” the physiological roles of the tubular ER network

Cited by 7 publications

References 116 publications

Atlastin 2/3 regulate ER targeting of the ULK1 complex to initiate autophagy

Atlastin 2/3 regulate ER targeting of the ULK1 complex to initiate autophagy

Algorithmic reconstruction of glioblastoma network complexity

Short-Term Omega-3 Supplementation Modulates Novel Neurovascular and Fatty Acid Metabolic Proteome Changes in the Retina and Ophthalmic Artery of Mice with Targeted Cyp2c44 Gene Deletion

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