Cell Competition Is Driven by Autophagy

Nagata, Rina; Nakamura, Mitsuki; Sanaki, Yuya; Igaki, Tatsushi

doi:10.1016/j.devcel.2019.08.018

Cited by 66 publications

(90 citation statements)

References 55 publications

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“…Previous studies using RNAi knock-down experiments indicate that Vha100-2 is involved in the development of multiple fly tissues (Wang et al, 2014;Overend et al, 2016;Mondragon et al, 2019;Nagata et al, 2019). We find that Vha100-2 is the sole isoform required for wing cuticle integrity.…”

Section: Discussionsupporting

confidence: 51%

“…Loss of Vha100-1 leads to vesicle accumulation in synaptic terminals (Wang et al, 2014), neuronal degeneration (Williamson et al, 2010a), and defects in brain wiring (Williamson et al, 2010b). RNAi knock-down experiments indicate that Vha100-2 is involved in regulation of neural stem cells proliferation (Wissel et al, 2018), acid generation of the midgut (Overend et al, 2016), elimination of nurse cells in the ovary (Mondragon et al, 2019), and cell competition in the eye disk (Nagata et al, 2019). Similar as Vha100-2, knock-down of Vha100-4 also leads to acidification defect in the larval midgut (Overend et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Investigation of Isoform Specific Functions of the V-ATPase a Subunit During Drosophila Wing Development

Chen

Jiang

et al. 2020

Front. Genet.

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The vacuolar ATPases (V-ATPases) are ATP-dependent proton pumps that play vital roles in eukaryotic cells. Insect V-ATPases are required in nearly all epithelial tissues to regulate a multiplicity of processes including receptor-mediated endocytosis, protein degradation, fluid secretion, and neurotransmission. Composed of fourteen different subunits, several V-ATPase subunits exist in distinct isoforms to perform cell type specific functions. The 100 kD a subunit (Vha100) of V-ATPases are encoded by a family of five genes in Drosophila, but their assignments are not fully understood. Here we report an experimental survey of the Vha100 gene family during Drosophila wing development. A combination of CRISPR-Cas9 mutagenesis, somatic clonal analysis and in vivo RNAi assays is used to characterize the requirement of Vha100 isoforms, and mutants of Vha100-2, Vha100-3, Vha100-4, and Vha100-5 genes were generated. We show that Vha100-3 and Vha100-5 are dispensable for fly development, while Vha100-1 is not critically required in the wing. As for the other two isoforms, we find that Vha100-2 regulates wing cuticle maturation, while Vha100-4 is the single isoform involved in developmental patterning. More specifically, Vha100-4 is required for proper activation of the Wingless signaling pathway during fly wing development. Interestingly, we also find a specific genetic interaction between Vha100-1 and Vha100-4 during wing development. Our results revealed the distinct roles of Vha100 isoforms during insect wing development, providing a rationale for understanding the diverse roles of V-ATPases.

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Section: Discussionsupporting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Investigation of Isoform Specific Functions of the V-ATPase a Subunit During Drosophila Wing Development

Chen

Jiang

et al. 2020

Front. Genet.

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“…In our study, WgGal4-driven overexpression of Atg8-mCherry and simultaneous knockdown of Klp98A induced early larval lethality, indicating that developmental autophagic processes in Wg-expressing cells also depend on Klp98A. During Drosophila eye development, autophagy was recently found to drive cell competition (Nagata et al, 2019). Given that neither larval growth nor wing development was perturbed by Klp98A knockdown alone, apical to basal transport of MVEs during wing imaginal disc development represents a new autophagy-independent function of Klp98A.…”

Section: Discussionmentioning

confidence: 59%

The kinesin motor Klp98A mediates apical to basal Wg transport

Witte¹,

Linnemannstöns²,

Schmidt³

et al. 2020

Development

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Development and tissue homeostasis rely on the tight regulation of morphogen secretion. In the Drosophila wing imaginal disc epithelium, Wg secretion for long-range signal transduction occurs after apical Wg entry into the endosomal system, followed by secretory endosomal transport. Although Wg release appears to occur from the apical and basal cell sides, its exact post-endocytic fate and the functional relevance of polarized endosomal Wg trafficking are poorly understood. Here, we identify the kinesin-3 family member Klp98A as the master regulator of intracellular Wg transport after apical endocytosis. In the absence of Klp98A, functional mature endosomes accumulate in the apical cytosol, and endosome transport to the basal cytosol is perturbed. Despite the resulting Wg mislocalization, Wg signal transduction occurs normally. We conclude that transcytosis-independent routes for Wg trafficking exist and demonstrate that Wg can be recycled apically via Rab4-recycling endosomes in the absence of Klp98A.

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“…As circulating arginine is degraded by the arginase ARG1, which is released into blood flow due to liver damage in autophagy-deficient host mice, tumorigenesis in mice with autophagy knockout in each tissue may differ from mice with systemic loss of autophagy. Alternatively, autophagy in loser cells supports their elimination during cell competition 126 , which may cause selection pressure toward an expanded population of autophagy-deficient cells in a microenvironment involving heterogeneous autophagic activity, including model mice generated by an approach involving Cre recombinase. These non-cell autonomous factors need to be taken into account to determine the effect of systemic changes in autophagy in future studies.…”

Section: Tumorigenesismentioning

confidence: 99%

Autophagosome biogenesis and human health

Kawabata

Yoshimori

2020

Cell Discov

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Autophagy degrades the cytoplasmic contents engulfed by autophagosomes. Besides providing energy and building blocks during starvation via random degradation, autophagy selectively targets cytotoxic components to prevent a wide range of diseases. This preventive activity of autophagy is supported by many studies using animal models and reports identifying several mutations in autophagy-related genes that are associated with human genetic disorders, which have been published in the past decade. Here, we summarize the molecular mechanisms of autophagosome biogenesis involving the proteins responsible for these genetic disorders, demonstrating a role for autophagy in human health. These findings will help elucidate the underlying mechanisms of autophagy-related diseases and develop future medications.

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Cell Competition Is Driven by Autophagy

Abstract: Highlights d Autophagy is required for losers of cell competition to be eliminated d Autophagy is elevated in prospective loser cells nearby winner cells d Elevated autophagy induces hid expression via NFkB d Hid cooperates with JNK signaling in loser cells to induce cell death

Cited by 66 publications

References 55 publications

Investigation of Isoform Specific Functions of the V-ATPase a Subunit During Drosophila Wing Development

Investigation of Isoform Specific Functions of the V-ATPase a Subunit During Drosophila Wing Development

The kinesin motor Klp98A mediates apical to basal Wg transport

Autophagosome biogenesis and human health

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