The class III PI(3)K Vps34 promotes autophagy and endocytosis but not TOR signaling in Drosophila

G. Juhász, Jahda H. Hill, Ying Yan, M. Sass, Eric H. Baehrecke, Jonathan M. Backer, Thomas P. Neufeld

Research output: Contribution to journalArticle

235 Citations (Scopus)

Abstract

Degradation of cytoplasmic components by autophagy requires the class III phosphatidylinositol 3 (PI(3))-kinase Vps34, but the mechanisms by which this kinase and its lipid product PI(3) phosphate (PI(3)P) promote autophagy are unclear. In mammalian cells, Vps34, with the proautophagic tumor suppressors Beclin1/Atg6, Bif-1, and UVRAG, forms a multiprotein complex that initiates autophagosome formation. Distinct Vps34 complexes also regulate endocytic processes that are critical for late-stage autophagosome-lysosome fusion. In contrast, Vps34 may also transduce activating nutrient signals to mammalian target of rapamycin (TOR), a negative regulator of autophagy. To determine potential in vivo functions of Vps34, we generated mutations in the single Drosophila melanogaster Vps34 orthologue, causing cell-autonomous disruption of autophagosome/ autolysosome formation in larval fat body cells. Endocytosis is also disrupted in Vps34-/- animals, but we demonstrate that this does not account for their autophagy defect. Unexpectedly, TOR signaling is unaffected in Vps34 mutants, indicating that Vps34 does not act upstream of TOR in this system. Instead, we show that TOR/Atg1 signaling regulates the starvation-induced recruitment of PI(3)P to nascent autophagosomes. Our results suggest that Vps34 is regulated by TOR-dependent nutrient signals directly at sites of autophagosome formation.

Original languageEnglish
Pages (from-to)655-666
Number of pages12
JournalJournal of Cell Biology
Volume181
Issue number4
DOIs
Publication statusPublished - May 19 2008

Fingerprint

Autophagy
Sirolimus
Phosphatidylinositols
Endocytosis
Drosophila
Class III Phosphatidylinositol 3-Kinases
Multiprotein Complexes
Food
Fat Body
Starvation
Lysosomes
Drosophila melanogaster
Adipocytes
Phosphotransferases
Autophagosomes
Lipids
Mutation
Neoplasms

ASJC Scopus subject areas

  • Cell Biology

Cite this

The class III PI(3)K Vps34 promotes autophagy and endocytosis but not TOR signaling in Drosophila. / Juhász, G.; Hill, Jahda H.; Yan, Ying; Sass, M.; Baehrecke, Eric H.; Backer, Jonathan M.; Neufeld, Thomas P.

In: Journal of Cell Biology, Vol. 181, No. 4, 19.05.2008, p. 655-666.

Research output: Contribution to journalArticle

Juhász, G. ; Hill, Jahda H. ; Yan, Ying ; Sass, M. ; Baehrecke, Eric H. ; Backer, Jonathan M. ; Neufeld, Thomas P. / The class III PI(3)K Vps34 promotes autophagy and endocytosis but not TOR signaling in Drosophila. In: Journal of Cell Biology. 2008 ; Vol. 181, No. 4. pp. 655-666.
@article{134c81fd627247f595c74ec60a90d38e,
title = "The class III PI(3)K Vps34 promotes autophagy and endocytosis but not TOR signaling in Drosophila",
abstract = "Degradation of cytoplasmic components by autophagy requires the class III phosphatidylinositol 3 (PI(3))-kinase Vps34, but the mechanisms by which this kinase and its lipid product PI(3) phosphate (PI(3)P) promote autophagy are unclear. In mammalian cells, Vps34, with the proautophagic tumor suppressors Beclin1/Atg6, Bif-1, and UVRAG, forms a multiprotein complex that initiates autophagosome formation. Distinct Vps34 complexes also regulate endocytic processes that are critical for late-stage autophagosome-lysosome fusion. In contrast, Vps34 may also transduce activating nutrient signals to mammalian target of rapamycin (TOR), a negative regulator of autophagy. To determine potential in vivo functions of Vps34, we generated mutations in the single Drosophila melanogaster Vps34 orthologue, causing cell-autonomous disruption of autophagosome/ autolysosome formation in larval fat body cells. Endocytosis is also disrupted in Vps34-/- animals, but we demonstrate that this does not account for their autophagy defect. Unexpectedly, TOR signaling is unaffected in Vps34 mutants, indicating that Vps34 does not act upstream of TOR in this system. Instead, we show that TOR/Atg1 signaling regulates the starvation-induced recruitment of PI(3)P to nascent autophagosomes. Our results suggest that Vps34 is regulated by TOR-dependent nutrient signals directly at sites of autophagosome formation.",
author = "G. Juh{\'a}sz and Hill, {Jahda H.} and Ying Yan and M. Sass and Baehrecke, {Eric H.} and Backer, {Jonathan M.} and Neufeld, {Thomas P.}",
year = "2008",
month = "5",
day = "19",
doi = "10.1083/jcb.200712051",
language = "English",
volume = "181",
pages = "655--666",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "4",

}

TY - JOUR

T1 - The class III PI(3)K Vps34 promotes autophagy and endocytosis but not TOR signaling in Drosophila

AU - Juhász, G.

AU - Hill, Jahda H.

AU - Yan, Ying

AU - Sass, M.

AU - Baehrecke, Eric H.

AU - Backer, Jonathan M.

AU - Neufeld, Thomas P.

PY - 2008/5/19

Y1 - 2008/5/19

N2 - Degradation of cytoplasmic components by autophagy requires the class III phosphatidylinositol 3 (PI(3))-kinase Vps34, but the mechanisms by which this kinase and its lipid product PI(3) phosphate (PI(3)P) promote autophagy are unclear. In mammalian cells, Vps34, with the proautophagic tumor suppressors Beclin1/Atg6, Bif-1, and UVRAG, forms a multiprotein complex that initiates autophagosome formation. Distinct Vps34 complexes also regulate endocytic processes that are critical for late-stage autophagosome-lysosome fusion. In contrast, Vps34 may also transduce activating nutrient signals to mammalian target of rapamycin (TOR), a negative regulator of autophagy. To determine potential in vivo functions of Vps34, we generated mutations in the single Drosophila melanogaster Vps34 orthologue, causing cell-autonomous disruption of autophagosome/ autolysosome formation in larval fat body cells. Endocytosis is also disrupted in Vps34-/- animals, but we demonstrate that this does not account for their autophagy defect. Unexpectedly, TOR signaling is unaffected in Vps34 mutants, indicating that Vps34 does not act upstream of TOR in this system. Instead, we show that TOR/Atg1 signaling regulates the starvation-induced recruitment of PI(3)P to nascent autophagosomes. Our results suggest that Vps34 is regulated by TOR-dependent nutrient signals directly at sites of autophagosome formation.

AB - Degradation of cytoplasmic components by autophagy requires the class III phosphatidylinositol 3 (PI(3))-kinase Vps34, but the mechanisms by which this kinase and its lipid product PI(3) phosphate (PI(3)P) promote autophagy are unclear. In mammalian cells, Vps34, with the proautophagic tumor suppressors Beclin1/Atg6, Bif-1, and UVRAG, forms a multiprotein complex that initiates autophagosome formation. Distinct Vps34 complexes also regulate endocytic processes that are critical for late-stage autophagosome-lysosome fusion. In contrast, Vps34 may also transduce activating nutrient signals to mammalian target of rapamycin (TOR), a negative regulator of autophagy. To determine potential in vivo functions of Vps34, we generated mutations in the single Drosophila melanogaster Vps34 orthologue, causing cell-autonomous disruption of autophagosome/ autolysosome formation in larval fat body cells. Endocytosis is also disrupted in Vps34-/- animals, but we demonstrate that this does not account for their autophagy defect. Unexpectedly, TOR signaling is unaffected in Vps34 mutants, indicating that Vps34 does not act upstream of TOR in this system. Instead, we show that TOR/Atg1 signaling regulates the starvation-induced recruitment of PI(3)P to nascent autophagosomes. Our results suggest that Vps34 is regulated by TOR-dependent nutrient signals directly at sites of autophagosome formation.

UR - http://www.scopus.com/inward/record.url?scp=44149127993&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=44149127993&partnerID=8YFLogxK

U2 - 10.1083/jcb.200712051

DO - 10.1083/jcb.200712051

M3 - Article

VL - 181

SP - 655

EP - 666

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 4

ER -