An Endoplasmic Reticulum ATPase Safeguards Endoplasmic Reticulum Identity by Removing Ectopically Localized Mitochondrial Proteins

Qin, Qing; Zhao, Ting; Zou, Wei; Shen, Kang; Wang, Xiangming

doi:10.1016/j.celrep.2020.108363

Cited by 36 publications

(42 citation statements)

References 49 publications

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“…Therefore, catp-8 may be involved in the insertion/localization of certain transmembrane proteins but not others to the plasma membrane. These findings are consistent with another recent study showing similar effects on DMA-1::GFP [23,24], although it was also reported by Qin et al that the levels of a HPO-30 reporter remained unchanged [24]. A possible explanation for this discrepancy is that we measured fluorescence in distal dendrites rather than the cell body [24].…”

Section: Substrates Of the Catp-8/p5a-atpasesupporting

confidence: 93%

“…First, genetic manipulations in C. elegans that suppress ER defects in PVD as a result of the mislocalized DRP-1/Drp1 mitochondrial fission protein to the ER in catp-8 mutants, fail to restore the correct dendritic morphology [24] suggesting that catp-8/P5A-ATPase serves additional functions beyond maintaining ER integrity to mediate PVD morphogenesis. Second, proteomic studies in HeLa cells found not only the levels of mitochondrial, but also other transmembrane and secreted proteins changed in ATP13A1/P5A-ATPAse mutant cells.…”

Section: Substrates Of the Catp-8/p5a-atpasementioning

confidence: 99%

“…Taken together, these results suggest that the CATP-8/P5A-ATPase functions in multiple pathways during neural patterning and is important for correct localization of transmembrane cell surface proteins. While this study was in progress, two studies reporting a function for catp-8/P5A-ATPase in PVD patterning in C. elegans were published [23,24]. Feng et al suggested a role for catp-8/P5A-ATPase in targeting of DMA-1/LRR-TM in dendrites [23] and Qin et al suggested that catp-8 was important for ER homeostasis by preventing mistargeting of mitochondrial proteins independently of ERassociated degradation (ERAD) [24].…”

Section: Introductionmentioning

confidence: 96%

“…While this study was in progress, two studies reporting a function for catp-8/P5A-ATPase in PVD patterning in C. elegans were published [23,24]. Feng et al suggested a role for catp-8/P5A-ATPase in targeting of DMA-1/LRR-TM in dendrites [23] and Qin et al suggested that catp-8 was important for ER homeostasis by preventing mistargeting of mitochondrial proteins independently of ERassociated degradation (ERAD) [24]. Similarly, a crystal structure of the yeast homolog Spf1 in conjunction with biochemical studies suggested a role for P5A-ATPases in ER and mitochondrial quality control [25].…”

Section: Introductionmentioning

confidence: 99%

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The CATP-8/P5A-type ATPase functions in multiple pathways during neuronal patterning

Tang

Trivedi

Freund

et al. 2021

Preprint

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The assembly of neuronal circuits involves the migrations of neurons from their place of birth to their final location in the nervous system, as well as the coordinated growth and patterning of axons and dendrites. In screens for genes required for patterning of the nervous system, we identified the catp-8/P5A-ATPase as an important regulator of neural patterning. P5A-ATPases are part of the P-type ATPases, a family of proteins known to serve a conserved function as transporters of ions, lipids and polyamines in unicellular eukaryotes, plants, and humans. While the function of many P-type ATPases is relatively well understood, the function of P5A-ATPases in metazoans remained elusive. We show here, that the Caenorhabditis elegans ortholog catp-8/P5A-ATPase is required for specific aspects of nervous system development. Specifically, the catp-8/P5A-ATPase serves functions in shaping the elaborately sculpted dendritic trees of somatosensory PVD neurons. Moreover, catp-8/P5A-ATPase is required for axonal guidance and repulsion at the midline, as well as embryonic and postembryonic neuronal migrations. Interestingly, not all axons at the midline require catp-8/P5A-ATPase , although the axons run in the same fascicles and navigate the same space. Similarly, not all neuronal migrations require catp-8/P5A-ATPase . A CATP -8/P5A-ATPase reporter is localized to the ER in most if not all tissues and catp-8/P5A-ATPase can function both cell-autonomously and non-autonomously to regulate neuronal development. Genetic analyses establish that catp-8/P5A-ATPase can function in multiple pathways, including the Menorin pathway, previously shown to control dendritic patterning in PVD, and Wnt signaling, which functions to control neuronal migrations. Lastly, we show that catp-8/P5A-ATPase is required for localizing select transmembrane proteins necessary for dendrite morphogenesis. Collectively, our studies suggest that catp-8/P5A-ATPase serves diverse, yet specific roles in different genetic pathways, and may be involved in the regulation or localization of transmembrane proteins to specific subcellular compartments.

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Section: Substrates Of the Catp-8/p5a-atpasesupporting

confidence: 93%

Section: Substrates Of the Catp-8/p5a-atpasementioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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The CATP-8/P5A-type ATPase functions in multiple pathways during neuronal patterning

Tang

Trivedi

Freund

et al. 2021

Preprint

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“…2Autophagy was shown to play an important role in clearing off non-productive proteins from the ER surface (Loi et al, 2019;Schäfer et al, 2020). 3Two recent studies discovered the ER protein Spf1 (P5A-ATPase in mammals) as a transmembrane helix dislocase that extracts missorted mitochondrial tail-anchored proteins from the ER membrane (McKenna et al, 2020;Qin et al, 2020). Interestingly, Spf1 was among the proteins that we coisolated with Ema19-GFP (see Fig.…”

Section: Discussionmentioning

confidence: 88%

The ER protein Ema19 facilitates the degradation of nonimported mitochondrial precursor proteins

Laborenz

Bykov

Knöringer

et al. 2021

MBoC

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For the biogenesis of mitochondria, hundreds of proteins need to be targeted from the cytosol into the various compartments of this organelle. The intramitochondrial targeting routes these proteins take to reach their respective location in the organelle are well understood. However, the early targeting processes, from cytosolic ribosomes to the membrane of the organelle, are still largely unknown. In this study, we present evidence that an integral membrane protein of the endoplasmic reticulum (ER), Ema19, plays a role in this process. Mutants lacking Ema19 show an increased stability of mitochondrial precursor proteins, indicating that Ema19 promotes the proteolytic degradation of non-productive precursors. The deletion of Ema19 improves the growth of respiration-deficient cells, suggesting that Ema19-mediated degradation can compete with productive protein import into mitochondria. Ema19 is the yeast representative of a conserved protein family. The human Ema19 homolog is known as sigma 2 receptor or TMEM97. Though its molecular function is not known, previous studies suggested a role of the sigma 2 receptor as a quality control factor in the ER, compatible with our observations about Ema19. More globally, our data provide an additional demonstration of the important role of the ER in mitochondrial protein targeting.

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The involvement of the mitochondrial membrane in drug delivery

Huang,

Ji,

Zhang

et al. 2024

Acta Biomaterialia

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An Endoplasmic Reticulum ATPase Safeguards Endoplasmic Reticulum Identity by Removing Ectopically Localized Mitochondrial Proteins

Cited by 36 publications

References 49 publications

The CATP-8/P5A-type ATPase functions in multiple pathways during neuronal patterning

The CATP-8/P5A-type ATPase functions in multiple pathways during neuronal patterning

The ER protein Ema19 facilitates the degradation of nonimported mitochondrial precursor proteins

The involvement of the mitochondrial membrane in drug delivery

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