NRBF2 regulates macroautophagy as a component of Vps34 complex I

Yanyan Cao, Yichen Wang, Widian F. Abi Saab, Fajun Yang, Jeffrey E. Pessin, Jonathan M. Backer

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Macroautophagy is a physiological cellular response to nutrient stress, which leads to the engulfment of cytosolic contents by a double-walledmembrane structure, the phagophore. Phagophores seal to become autophagosomes, which then fuse with lysosomes to deliver their contents for degradation. Macroautophagy is regulated by numerous cellular factors, including the Class III PI3K (phosphoinositide 3-kinase) Vps34 (vacuolar protein sorting 34). The autophagic functions of Vps34 require its recruitment to a complex that includes Vps15, Beclin-1 and Atg14L (autophagy-related 14-like protein) and is known as Vps34 Complex I. We have now identified NRBF2 (nuclear receptor-binding factor 2) as a new member of Vps34 Complex I. NRBF2 binds to complexes that include Vps34, Vps15, Beclin-1 and ATG-14L, but not the Vps34 Complex II component UVRAG (UV radiation resistance-associated gene). NRBF2 directly interacts with Vps15 via the Vps15 WD40 domain as well as other regions of Vps15. The formation of GFP-LC3 (light chain 3) punctae and PE (phosphatidylethanolamine)-conjugated LC3 (LC3-II) in serum-starved cells was inhibited by NRBF2 knockdown in the absence and presence of lysosomal inhibitors, and p62 levels were increased. Thus NRBF2 plays a critical role in the induction of starvation-induced autophagy as a specific member of Vps34 Complex I.

Original languageEnglish (US)
Pages (from-to)315-322
Number of pages8
JournalBiochemical Journal
Volume461
Issue number2
DOIs
StatePublished - Jul 15 2014

Fingerprint

Autophagy
Protein Transport
Cytoplasmic and Nuclear Receptors
Sorting
Proteins
1-Phosphatidylinositol 4-Kinase
Starvation
Lysosomes
Electric fuses
Phosphatidylinositols
Ultraviolet radiation
Nutrients
Seals
Radiation
Phosphotransferases
Genes
Light
Food
Degradation
Serum

Keywords

  • Autophagy
  • Human vacuolar protein sorting 34 (hVps34)
  • Macroautophagy
  • Mass spectrometry
  • Nuclear receptor-binding factor 2 (NRBF2)
  • Vacuolar protein sorting 15 (Vps15)
  • Vacuolar protein sorting 34 (Vps34)

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

NRBF2 regulates macroautophagy as a component of Vps34 complex I. / Cao, Yanyan; Wang, Yichen; Abi Saab, Widian F.; Yang, Fajun; Pessin, Jeffrey E.; Backer, Jonathan M.

In: Biochemical Journal, Vol. 461, No. 2, 15.07.2014, p. 315-322.

Research output: Contribution to journalArticle

Cao, Yanyan ; Wang, Yichen ; Abi Saab, Widian F. ; Yang, Fajun ; Pessin, Jeffrey E. ; Backer, Jonathan M. / NRBF2 regulates macroautophagy as a component of Vps34 complex I. In: Biochemical Journal. 2014 ; Vol. 461, No. 2. pp. 315-322.
@article{b75ea9cbccc74e0c8fd3f28b9ce4c6a4,
title = "NRBF2 regulates macroautophagy as a component of Vps34 complex I",
abstract = "Macroautophagy is a physiological cellular response to nutrient stress, which leads to the engulfment of cytosolic contents by a double-walledmembrane structure, the phagophore. Phagophores seal to become autophagosomes, which then fuse with lysosomes to deliver their contents for degradation. Macroautophagy is regulated by numerous cellular factors, including the Class III PI3K (phosphoinositide 3-kinase) Vps34 (vacuolar protein sorting 34). The autophagic functions of Vps34 require its recruitment to a complex that includes Vps15, Beclin-1 and Atg14L (autophagy-related 14-like protein) and is known as Vps34 Complex I. We have now identified NRBF2 (nuclear receptor-binding factor 2) as a new member of Vps34 Complex I. NRBF2 binds to complexes that include Vps34, Vps15, Beclin-1 and ATG-14L, but not the Vps34 Complex II component UVRAG (UV radiation resistance-associated gene). NRBF2 directly interacts with Vps15 via the Vps15 WD40 domain as well as other regions of Vps15. The formation of GFP-LC3 (light chain 3) punctae and PE (phosphatidylethanolamine)-conjugated LC3 (LC3-II) in serum-starved cells was inhibited by NRBF2 knockdown in the absence and presence of lysosomal inhibitors, and p62 levels were increased. Thus NRBF2 plays a critical role in the induction of starvation-induced autophagy as a specific member of Vps34 Complex I.",
keywords = "Autophagy, Human vacuolar protein sorting 34 (hVps34), Macroautophagy, Mass spectrometry, Nuclear receptor-binding factor 2 (NRBF2), Vacuolar protein sorting 15 (Vps15), Vacuolar protein sorting 34 (Vps34)",
author = "Yanyan Cao and Yichen Wang and {Abi Saab}, {Widian F.} and Fajun Yang and Pessin, {Jeffrey E.} and Backer, {Jonathan M.}",
year = "2014",
month = "7",
day = "15",
doi = "10.1042/BJ20140515",
language = "English (US)",
volume = "461",
pages = "315--322",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "2",

}

TY - JOUR

T1 - NRBF2 regulates macroautophagy as a component of Vps34 complex I

AU - Cao, Yanyan

AU - Wang, Yichen

AU - Abi Saab, Widian F.

AU - Yang, Fajun

AU - Pessin, Jeffrey E.

AU - Backer, Jonathan M.

PY - 2014/7/15

Y1 - 2014/7/15

N2 - Macroautophagy is a physiological cellular response to nutrient stress, which leads to the engulfment of cytosolic contents by a double-walledmembrane structure, the phagophore. Phagophores seal to become autophagosomes, which then fuse with lysosomes to deliver their contents for degradation. Macroautophagy is regulated by numerous cellular factors, including the Class III PI3K (phosphoinositide 3-kinase) Vps34 (vacuolar protein sorting 34). The autophagic functions of Vps34 require its recruitment to a complex that includes Vps15, Beclin-1 and Atg14L (autophagy-related 14-like protein) and is known as Vps34 Complex I. We have now identified NRBF2 (nuclear receptor-binding factor 2) as a new member of Vps34 Complex I. NRBF2 binds to complexes that include Vps34, Vps15, Beclin-1 and ATG-14L, but not the Vps34 Complex II component UVRAG (UV radiation resistance-associated gene). NRBF2 directly interacts with Vps15 via the Vps15 WD40 domain as well as other regions of Vps15. The formation of GFP-LC3 (light chain 3) punctae and PE (phosphatidylethanolamine)-conjugated LC3 (LC3-II) in serum-starved cells was inhibited by NRBF2 knockdown in the absence and presence of lysosomal inhibitors, and p62 levels were increased. Thus NRBF2 plays a critical role in the induction of starvation-induced autophagy as a specific member of Vps34 Complex I.

AB - Macroautophagy is a physiological cellular response to nutrient stress, which leads to the engulfment of cytosolic contents by a double-walledmembrane structure, the phagophore. Phagophores seal to become autophagosomes, which then fuse with lysosomes to deliver their contents for degradation. Macroautophagy is regulated by numerous cellular factors, including the Class III PI3K (phosphoinositide 3-kinase) Vps34 (vacuolar protein sorting 34). The autophagic functions of Vps34 require its recruitment to a complex that includes Vps15, Beclin-1 and Atg14L (autophagy-related 14-like protein) and is known as Vps34 Complex I. We have now identified NRBF2 (nuclear receptor-binding factor 2) as a new member of Vps34 Complex I. NRBF2 binds to complexes that include Vps34, Vps15, Beclin-1 and ATG-14L, but not the Vps34 Complex II component UVRAG (UV radiation resistance-associated gene). NRBF2 directly interacts with Vps15 via the Vps15 WD40 domain as well as other regions of Vps15. The formation of GFP-LC3 (light chain 3) punctae and PE (phosphatidylethanolamine)-conjugated LC3 (LC3-II) in serum-starved cells was inhibited by NRBF2 knockdown in the absence and presence of lysosomal inhibitors, and p62 levels were increased. Thus NRBF2 plays a critical role in the induction of starvation-induced autophagy as a specific member of Vps34 Complex I.

KW - Autophagy

KW - Human vacuolar protein sorting 34 (hVps34)

KW - Macroautophagy

KW - Mass spectrometry

KW - Nuclear receptor-binding factor 2 (NRBF2)

KW - Vacuolar protein sorting 15 (Vps15)

KW - Vacuolar protein sorting 34 (Vps34)

UR - http://www.scopus.com/inward/record.url?scp=84903309911&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84903309911&partnerID=8YFLogxK

U2 - 10.1042/BJ20140515

DO - 10.1042/BJ20140515

M3 - Article

VL - 461

SP - 315

EP - 322

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 2

ER -