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Article ; Online: Hippo Signaling: Autophagy Waits in the Wings.

Neufeld, Thomas P

2020 Volume 52, Issue 5, Page(s) 544–545

Abstract: Crosstalk between signaling networks can help coordinate diverse cellular functions. In this issue of Developmental Cell, Tyra et al. identify connections between the cell-growth-promoting transcription factor YAP/Yorkie and the autophagy-regulating ... ...

Abstract	Crosstalk between signaling networks can help coordinate diverse cellular functions. In this issue of Developmental Cell, Tyra et al. identify connections between the cell-growth-promoting transcription factor YAP/Yorkie and the autophagy-regulating kinase Ulk1/Atg1.
MeSH term(s)	Animals ; Autophagy ; Phosphorylation ; Protein-Serine-Threonine Kinases ; Signal Transduction ; Wings, Animal
Chemical Substances	Protein-Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2020-03-24
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2054967-2
ISSN	1878-1551 ; 1534-5807
ISSN (online)	1878-1551
ISSN	1534-5807
DOI	10.1016/j.devcel.2020.02.014
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Zs.MG 76: Show issues

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Article ; Online: Autophagy and cell growth--the yin and yang of nutrient responses.

Neufeld, Thomas P

Journal of cell science

2012 Volume 125, Issue Pt 10, Page(s) 2359–2368

Abstract: As a response to nutrient deprivation and other cell stresses, autophagy is often induced in the context of reduced or arrested cell growth. A plethora of signaling molecules and pathways have been shown to have opposing effects on cell growth and ... ...

Abstract	As a response to nutrient deprivation and other cell stresses, autophagy is often induced in the context of reduced or arrested cell growth. A plethora of signaling molecules and pathways have been shown to have opposing effects on cell growth and autophagy, and results of recent functional screens on a genomic scale support the idea that these processes might represent mutually exclusive cell fates. Understanding the ways in which autophagy and cell growth relate to one another is becoming increasingly important, as new roles for autophagy in tumorigenesis and other growth-related phenomena are uncovered. This Commentary highlights recent findings that link autophagy and cell growth, and explores the mechanisms underlying these connections and their implications for cell physiology and survival. Autophagy and cell growth can inhibit one another through a variety of direct and indirect mechanisms, and can be independently regulated by common signaling pathways. The central role of the mammalian target of rapamycin (mTOR) pathway in regulating both autophagy and cell growth exemplifies one such mechanism. In addition, mTOR-independent signaling and other more direct connections between autophagy and cell growth will also be discussed.
MeSH term(s)	Animals ; Autophagy ; Cell Cycle ; Cell Proliferation ; Cells/cytology ; Cells/metabolism ; Humans ; Protein Biosynthesis ; Signal Transduction ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism
Chemical Substances	TOR Serine-Threonine Kinases (EC 2.7.1.1)
Language	English
Publishing date	2012-05-30
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
DOI	10.1242/jcs.103333
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Article ; Online: A Tissue- and Temporal-Specific Autophagic Switch Controls Drosophila Pre-metamorphic Nutritional Checkpoints.

Pan, Xueyang / Neufeld, Thomas P / O'Connor, Michael B

Current biology : CB

2019 Volume 29, Issue 17, Page(s) 2840–2851.e4

Abstract: Properly timed production of steroid hormones by endocrine tissues regulates juvenile-to-adult transitions in both mammals (puberty) and holometabolous insects (metamorphosis). Nutritional conditions influence the temporal control of the transition, but ... ...

Abstract	Properly timed production of steroid hormones by endocrine tissues regulates juvenile-to-adult transitions in both mammals (puberty) and holometabolous insects (metamorphosis). Nutritional conditions influence the temporal control of the transition, but the mechanisms responsible are ill defined. Here we demonstrate that autophagy acts as an endocrine organ-specific, nutritionally regulated gating mechanism to help ensure productive metamorphosis in Drosophila. Autophagy in the endocrine organ is specifically stimulated by nutrient restriction at the early, but not the late, third-instar larva stage. The timing of autophagy induction correlates with the nutritional checkpoints, which inhibit precocious metamorphosis during nutrient restriction in undersized larvae. Suppression of autophagy causes dysregulated pupariation of starved larvae, which leads to pupal lethality, whereas forced autophagy induction results in developmental delay/arrest in well-fed animals. Induction of autophagy disrupts production of the steroid hormone ecdysone at the time of pupariation not by destruction of hormone biosynthetic capacity but rather by limiting the availability of the steroid hormone precursor cholesterol in the endocrine cells via a lipophagy mechanism. Interestingly, autophagy in the endocrine organ functions by interacting with the endolysosome system, yet shows multiple features not fully consistent with a canonical autophagy process. Taken together, our findings demonstrate an autophagy mechanism in endocrine cells that helps shape the nutritional checkpoints and guarantee a successful juvenile-to-adult transition in animals confronting nutritional stress.
MeSH term(s)	Animal Nutritional Physiological Phenomena ; Animals ; Autophagy ; Drosophila melanogaster/growth & development ; Female ; Larva/growth & development ; Male ; Metamorphosis, Biological/physiology ; Pupa/growth & development
Language	English
Publishing date	2019-08-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1071731-6
ISSN	1879-0445 ; 0960-9822
ISSN (online)	1879-0445
ISSN	0960-9822
DOI	10.1016/j.cub.2019.07.027
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Article ; Online: Autophagosomes take the Klp98-A train.

Mauvezin, Caroline / Neufeld, Thomas P

Small GTPases

2016 Volume 8, Issue 1, Page(s) 16–19

Abstract: The intracellular movement of membrane-bound vesicles is closely tied to their formation, maturation and ultimate function within the cell. Motor proteins and their associated cytoskeletal networks are critical for vesicle transport, but whether these ... ...

Abstract	The intracellular movement of membrane-bound vesicles is closely tied to their formation, maturation and ultimate function within the cell. Motor proteins and their associated cytoskeletal networks are critical for vesicle transport, but whether these factors play a more direct role in vesicle biogenesis is unclear. In recent work, we found that the Drosophila kinesin proteins Khc and Klp98A are both required for the normal anterograde movement of autophagosomes and autolysosomes during starvation-induced autophagy. In addition, Klp98A has a transport-independent function of promoting autophagosome-lysosome fusion, a key step in the maturation of autophagic vesicles. This function correlates with the association of Klp98A with the autophagosomal protein Atg8 and with the endolysosomal protein Rab14, suggesting that Klp98A may promote vesicle fusion by physically linking these vesicle surface proteins. These findings demonstrate how the delivery of vesicles to their proper destination can be coordinated with additional steps in their life cycle through molecular motor-based interactions.
Language	English
Publishing date	2016-05-04
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2682247-7
ISSN	2154-1256 ; 2154-1248
ISSN (online)	2154-1256
ISSN	2154-1248
DOI	10.1080/21541248.2016.1184776
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Article ; Online: Atg1-independent induction of autophagy by the Drosophila Ulk3 homolog, ADUK.

Braden, Christopher R / Neufeld, Thomas P

The FEBS journal

2016 Volume 283, Issue 21, Page(s) 3889–3897

Abstract: Although canonical autophagy regulation requires a multi-protein complex centered on the Ser/Thr-kinase Atg1 (mammalian Ulk1/2), alternative signals can induce autophagy independent of Atg1 through unknown mechanisms. Here we identify the Drosophila Ulk3 ...

Abstract	Although canonical autophagy regulation requires a multi-protein complex centered on the Ser/Thr-kinase Atg1 (mammalian Ulk1/2), alternative signals can induce autophagy independent of Atg1 through unknown mechanisms. Here we identify the Drosophila Ulk3 ortholog, another Drosophila Unc-51-like kinase (ADUK), as an Atg1-independent autophagy inducer. ADUK interacts with Atg1 complex members Atg13 and 200 kDa FAK family kinase-interacting protein, and requires Atg13 but not Atg1 for autophagy induction. Loss of ADUK shortens adult lifespan and reduces the autophagic response to a chemical stressor, dimethyl sulfoxide. However, ADUK is not required for autophagy induction by Atg1-dependent nutrient or developmental cues. Atg1 and ADUK/Ulk3 thus represent alternative catalytic components of a shared autophagy kinase complex.
MeSH term(s)	Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Autophagy ; Autophagy-Related Protein-1 Homolog/classification ; Autophagy-Related Protein-1 Homolog/genetics ; Autophagy-Related Protein-1 Homolog/metabolism ; Autophagy-Related Proteins/genetics ; Autophagy-Related Proteins/metabolism ; Base Sequence ; Blotting, Western ; Drosophila Proteins/classification ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Female ; Male ; Microscopy, Confocal ; Mutation ; Phylogeny ; Protein Binding ; Protein-Serine-Threonine Kinases/classification ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/metabolism ; Signal Transduction
Chemical Substances	Atg13 protein, Drosophila ; Autophagy-Related Proteins ; Drosophila Proteins ; ADUK protein, Drosophila (EC 2.7.11.1) ; Atg1 protein, Drosophila (EC 2.7.11.1) ; Autophagy-Related Protein-1 Homolog (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2016-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.13906
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Article ; Online: Mechanical stress regulates insulin sensitivity through integrin-dependent control of insulin receptor localization.

Kim, Jung / Bilder, David / Neufeld, Thomas P

Genes & development

2018 Volume 32, Issue 2, Page(s) 156–164

Abstract: Insulin resistance, the failure to activate insulin signaling in the presence of ligand, leads to metabolic diseases, including type 2 diabetes. Physical activity and mechanical stress have been shown to protect against insulin resistance, but the ... ...

Abstract	Insulin resistance, the failure to activate insulin signaling in the presence of ligand, leads to metabolic diseases, including type 2 diabetes. Physical activity and mechanical stress have been shown to protect against insulin resistance, but the molecular mechanisms remain unclear. Here, we address this relationship in the
MeSH term(s)	Animals ; Cell Membrane ; Drosophila Proteins/metabolism ; Drosophila melanogaster/growth & development ; Drosophila melanogaster/metabolism ; Drosophila melanogaster/physiology ; Extracellular Matrix/metabolism ; Insulin/physiology ; Integrin beta Chains/metabolism ; Integrins/metabolism ; Larva/metabolism ; Movement ; Receptor, Insulin/metabolism ; Signal Transduction ; Stress, Mechanical ; TOR Serine-Threonine Kinases/metabolism ; Talin/metabolism
Chemical Substances	Drosophila Proteins ; Insulin ; Integrin beta Chains ; Integrins ; Talin ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Receptor, Insulin (EC 2.7.10.1)
Language	English
Publishing date	2018--15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	806684-x
ISSN	1549-5477 ; 0890-9369
ISSN (online)	1549-5477
ISSN	0890-9369
DOI	10.1101/gad.305870.117
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Zs.A 2292: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 54: Show issues

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Article ; Online: A STRIPAK complex mediates axonal transport of autophagosomes and dense core vesicles through PP2A regulation.

Neisch, Amanda L / Neufeld, Thomas P / Hays, Thomas S

The Journal of cell biology

2017 Volume 216, Issue 2, Page(s) 441–461

Abstract: Autophagy plays an essential role in the cellular homeostasis of neurons, facilitating the clearance of cellular debris. This clearance process is orchestrated through the assembly, transport, and fusion of autophagosomes with lysosomes for degradation. ... ...

Abstract	Autophagy plays an essential role in the cellular homeostasis of neurons, facilitating the clearance of cellular debris. This clearance process is orchestrated through the assembly, transport, and fusion of autophagosomes with lysosomes for degradation. The motor protein dynein drives autophagosome motility from distal sites of assembly to sites of lysosomal fusion. In this study, we identify the scaffold protein CKA (connector of kinase to AP-1) as essential for autophagosome transport in neurons. Together with other core components of the striatin-interacting phosphatase and kinase (STRIPAK) complex, we show that CKA associates with dynein and directly binds Atg8a, an autophagosomal protein. CKA is a regulatory subunit of PP2A, a component of the STRIPAK complex. We propose that the STRIPAK complex modulates dynein activity. Consistent with this hypothesis, we provide evidence that CKA facilitates axonal transport of dense core vesicles and autophagosomes in a PP2A-dependent fashion. In addition, CKA-deficient flies exhibit PP2A-dependent motor coordination defects. CKA function within the STRIPAK complex is crucial to prevent transport defects that may contribute to neurodegeneration.
MeSH term(s)	Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Animals, Genetically Modified ; Autophagosomes/enzymology ; Axonal Transport ; Axons/enzymology ; Cell Line ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Drosophila melanogaster/enzymology ; Drosophila melanogaster/genetics ; Dyneins/genetics ; Dyneins/metabolism ; Genotype ; Microscopy, Fluorescence ; Multiprotein Complexes/genetics ; Multiprotein Complexes/metabolism ; Mutation ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Phenotype ; Presynaptic Terminals/metabolism ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Phosphatase 2/genetics ; Protein Phosphatase 2/metabolism ; RNA Interference ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/metabolism ; Secretory Vesicles/enzymology ; Signal Transduction ; Transfection
Chemical Substances	Adaptor Proteins, Signal Transducing ; Atg8a protein, Drosophila ; Cka protein, Drosophila ; Drosophila Proteins ; Mob4 protein, Drosophila ; Multiprotein Complexes ; Nerve Tissue Proteins ; Recombinant Fusion Proteins ; mts protein, Drosophila ; Protein Phosphatase 2 (EC 3.1.3.16) ; Dyneins (EC 3.6.4.2)
Language	English
Publishing date	2017-01-18
Publishing country	United States
Document type	Journal Article ; Video-Audio Media
ZDB-ID	218154-x
ISSN	1540-8140 ; 0021-9525
ISSN (online)	1540-8140
ISSN	0021-9525
DOI	10.1083/jcb.201606082
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Article ; Online: Rab6 promotes insulin receptor and cathepsin trafficking to regulate autophagy induction and activity in

Ayala, Carlos I / Kim, Jung / Neufeld, Thomas P

Journal of cell science

2018 Volume 131, Issue 17

Abstract: The self-degradative process of autophagy is important for energy homeostasis and cytoplasmic renewal. This lysosome-mediated pathway is negatively regulated by the target of rapamycin kinase (TOR) under basal conditions, and requires the vesicle ... ...

Abstract	The self-degradative process of autophagy is important for energy homeostasis and cytoplasmic renewal. This lysosome-mediated pathway is negatively regulated by the target of rapamycin kinase (TOR) under basal conditions, and requires the vesicle trafficking machinery regulated by Rab GTPases. However, the interactions between autophagy, TOR and Rab proteins remain incompletely understood
MeSH term(s)	Animals ; Autophagy ; Cathepsin D/genetics ; Cathepsin D/metabolism ; Cell Membrane/genetics ; Cell Membrane/metabolism ; Drosophila/cytology ; Drosophila/genetics ; Drosophila/metabolism ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Lysosomes/genetics ; Lysosomes/metabolism ; Protein Transport ; Receptor Protein-Tyrosine Kinases/genetics ; Receptor Protein-Tyrosine Kinases/metabolism ; Signal Transduction ; rab GTP-Binding Proteins/genetics ; rab GTP-Binding Proteins/metabolism
Chemical Substances	Drosophila Proteins ; InR protein, Drosophila (EC 2.7.10.1) ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1) ; tor protein, Drosophila (EC 2.7.10.1) ; Cathepsin D (EC 3.4.23.5) ; Rab6 protein, Drosophila (EC 3.6.1.-) ; rab GTP-Binding Proteins (EC 3.6.5.2)
Language	English
Publishing date	2018-09-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
DOI	10.1242/jcs.216127
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Article ; Online: Dietary sugar promotes systemic TOR activation in Drosophila through AKH-dependent selective secretion of Dilp3.

Kim, Jung / Neufeld, Thomas P

Nature communications

2015 Volume 6, Page(s) 6846

Abstract: Secreted ligands of the insulin family promote cell growth and maintain sugar homeostasis. Insulin release is tightly regulated in response to dietary conditions, but how insulin-producing cells (IPCs) coordinate their responses to distinct nutrient ... ...

Abstract	Secreted ligands of the insulin family promote cell growth and maintain sugar homeostasis. Insulin release is tightly regulated in response to dietary conditions, but how insulin-producing cells (IPCs) coordinate their responses to distinct nutrient signals is unclear. Here we show that regulation of insulin secretion in Drosophila larvae has been segregated into distinct branches-whereas amino acids promote the secretion of Drosophila insulin-like peptide 2 (Dilp2), circulating sugars promote the selective release of Dilp3. Dilp3 is uniquely required for the sugar-mediated activation of TOR signalling and suppression of autophagy in the larval fat body. Sugar levels are not sensed directly by the IPCs, but rather by the adipokinetic hormone (AKH)-producing cells of the corpora cardiaca, and we demonstrate that AKH signalling is required in the IPCs for sugar-dependent Dilp3 release. Thus, IPCs integrate multiple cues to regulate the secretion of distinct insulin subtypes under varying nutrient conditions.
MeSH term(s)	Animals ; Autophagy ; Corpora Allata/cytology ; Corpora Allata/metabolism ; Dietary Sucrose/metabolism ; Drosophila Proteins/metabolism ; Drosophila melanogaster ; Insect Hormones/metabolism ; Insulin-Secreting Cells/metabolism ; Intercellular Signaling Peptides and Proteins/metabolism ; Larva ; Oligopeptides/metabolism ; Pyrrolidonecarboxylic Acid/analogs & derivatives ; Pyrrolidonecarboxylic Acid/metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism
Chemical Substances	Dietary Sucrose ; Drosophila Proteins ; ILP3 protein, Drosophila ; Insect Hormones ; Intercellular Signaling Peptides and Proteins ; Oligopeptides ; DAKH peptide (129204-82-6) ; target of rapamycin protein, Drosophila (EC 2.7.1.-) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Pyrrolidonecarboxylic Acid (SZB83O1W42)
Language	English
Publishing date	2015-04-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/ncomms7846
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Article ; Online: Bafilomycin A1 disrupts autophagic flux by inhibiting both V-ATPase-dependent acidification and Ca-P60A/SERCA-dependent autophagosome-lysosome fusion.

Mauvezin, Caroline / Neufeld, Thomas P

Autophagy

2015 Volume 11, Issue 8, Page(s) 1437–1438

Abstract: Autophagosome-lysosome fusion and autolysosome acidification constitute late steps in the autophagic process necessary to maintain functional autophagic flux and cellular homeostasis. Both of these steps are disrupted by the V-ATPase inhibitor ... ...

Abstract	Autophagosome-lysosome fusion and autolysosome acidification constitute late steps in the autophagic process necessary to maintain functional autophagic flux and cellular homeostasis. Both of these steps are disrupted by the V-ATPase inhibitor bafilomycin A1, but the mechanisms potentially linking them are unclear. We recently revisited the role of lysosomal acidification in autophagosome-lysosome fusion, using an in vivo approach in Drosophila. By genetically depleting individual subunits of the V-ATPase, we confirmed its role in lysosomal acidification and autophagic cargo degradation. Surprisingly, vesicle fusion remained active in V-ATPase-depleted cells, indicating that autophagosome-lysosome fusion and autolysosome acidification are 2 separable processes. In contrast, bafilomycin A1 inhibited both acidification and fusion, consistent with its effects in mammalian cells. Together, these results imply that this drug inhibits fusion independently of its effect on V-ATPase-mediated acidification. We identified the ER-calcium ATPase Ca-P60A/dSERCA as a novel target of bafilomycin A1. Autophagosome-lysosome fusion was defective in Ca-P60A/dSERCA-depleted cells, and bafilomycin A1 induced a significant increase in cytosolic calcium concentration and disrupted Ca-P60A/SERCA-mediated fusion. Thus, bafilomycin A1 disrupts autophagic flux by independently inhibiting V-ATPase-dependent acidification and Ca-P60A/SERCA-dependent autophagosome-lysosome fusion.
MeSH term(s)	Animals ; Autophagy ; Calcium/metabolism ; Drosophila/metabolism ; Endoplasmic Reticulum/metabolism ; Homeostasis ; Lysosomes/metabolism ; Macrolides/chemistry ; Membrane Fusion ; Phagosomes/metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism ; Signal Transduction ; Vacuolar Proton-Translocating ATPases/metabolism
Chemical Substances	Macrolides ; bafilomycin A1 (88899-55-2) ; Vacuolar Proton-Translocating ATPases (EC 3.6.1.-) ; Sarcoplasmic Reticulum Calcium-Transporting ATPases (EC 3.6.3.8) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2015-07-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2454135-7
ISSN	1554-8635 ; 1554-8627
ISSN (online)	1554-8635
ISSN	1554-8627
DOI	10.1080/15548627.2015.1066957
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