PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 transport by differential interactions with the ER tether and the beclin 1 complex

Shanshan He, Duojiao Ni, Binyun Ma, Joo Hyung Lee, Tian Zhang, Irene Ghozalli, Sara Dolatshahi Pirooz, Zhen Zhao, Nagakumar Bharatham, Baihong Li, Soohwan Oh, Wen Hwa Lee, Yoshinori Takahashi, Hong-Gang Wang, Arlet Minassian, Pinghui Feng, Vojo Deretic, Rainer Pepperkok, Mitsuo Tagaya, Ho Sup YoonChengyu Liang

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Endoplasmic reticulum (ER)-Golgi membrane transport and autophagy are intersecting trafficking pathways that are tightly regulated and crucial for homeostasis, development and disease. Here, we identify UVRAG, a beclin-1-binding autophagic factor, as a phosphatidylinositol-3-phosphate (PtdIns(3)P)-binding protein that depends on PtdIns(3)P for its ER localization. We further show that UVRAG interacts with RINT-1, and acts as an integral component of the RINT-1-containing ER tethering complex, which couples phosphoinositide metabolism to COPI-vesicle tethering. Displacement or knockdown of UVRAG profoundly disrupted COPI cargo transfer to the ER and Golgi integrity. Intriguingly, autophagy caused the dissociation of UVRAG from the ER tether, which in turn worked in concert with the Bif-1-beclin-1-PI(3)KC3 complex to mobilize Atg9 translocation for autophagosome formation. These findings identify a regulatory mechanism that coordinates Golgi-ER retrograde and autophagy-related vesicular trafficking events through physical and functional interactions between UVRAG, phosphoinositide and their regulatory factors, thereby ensuring spatiotemporal fidelity of membrane trafficking and maintenance of organelle homeostasis.

Original languageEnglish (US)
Pages (from-to)1206-1219
Number of pages14
JournalNature Cell Biology
Volume15
Issue number10
DOIs
StatePublished - Oct 1 2013

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Endoplasmic Reticulum
Autophagy
Coat Protein Complex I
Phosphatidylinositols
Phosphate-Binding Proteins
Homeostasis
Membranes
Organelles
Beclin-1
phosphatidylinositol 3-phosphate
Maintenance

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

He, Shanshan ; Ni, Duojiao ; Ma, Binyun ; Lee, Joo Hyung ; Zhang, Tian ; Ghozalli, Irene ; Pirooz, Sara Dolatshahi ; Zhao, Zhen ; Bharatham, Nagakumar ; Li, Baihong ; Oh, Soohwan ; Lee, Wen Hwa ; Takahashi, Yoshinori ; Wang, Hong-Gang ; Minassian, Arlet ; Feng, Pinghui ; Deretic, Vojo ; Pepperkok, Rainer ; Tagaya, Mitsuo ; Yoon, Ho Sup ; Liang, Chengyu. / PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 transport by differential interactions with the ER tether and the beclin 1 complex. In: Nature Cell Biology. 2013 ; Vol. 15, No. 10. pp. 1206-1219.
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abstract = "Endoplasmic reticulum (ER)-Golgi membrane transport and autophagy are intersecting trafficking pathways that are tightly regulated and crucial for homeostasis, development and disease. Here, we identify UVRAG, a beclin-1-binding autophagic factor, as a phosphatidylinositol-3-phosphate (PtdIns(3)P)-binding protein that depends on PtdIns(3)P for its ER localization. We further show that UVRAG interacts with RINT-1, and acts as an integral component of the RINT-1-containing ER tethering complex, which couples phosphoinositide metabolism to COPI-vesicle tethering. Displacement or knockdown of UVRAG profoundly disrupted COPI cargo transfer to the ER and Golgi integrity. Intriguingly, autophagy caused the dissociation of UVRAG from the ER tether, which in turn worked in concert with the Bif-1-beclin-1-PI(3)KC3 complex to mobilize Atg9 translocation for autophagosome formation. These findings identify a regulatory mechanism that coordinates Golgi-ER retrograde and autophagy-related vesicular trafficking events through physical and functional interactions between UVRAG, phosphoinositide and their regulatory factors, thereby ensuring spatiotemporal fidelity of membrane trafficking and maintenance of organelle homeostasis.",
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He, S, Ni, D, Ma, B, Lee, JH, Zhang, T, Ghozalli, I, Pirooz, SD, Zhao, Z, Bharatham, N, Li, B, Oh, S, Lee, WH, Takahashi, Y, Wang, H-G, Minassian, A, Feng, P, Deretic, V, Pepperkok, R, Tagaya, M, Yoon, HS & Liang, C 2013, 'PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 transport by differential interactions with the ER tether and the beclin 1 complex', Nature Cell Biology, vol. 15, no. 10, pp. 1206-1219. https://doi.org/10.1038/ncb2848

PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 transport by differential interactions with the ER tether and the beclin 1 complex. / He, Shanshan; Ni, Duojiao; Ma, Binyun; Lee, Joo Hyung; Zhang, Tian; Ghozalli, Irene; Pirooz, Sara Dolatshahi; Zhao, Zhen; Bharatham, Nagakumar; Li, Baihong; Oh, Soohwan; Lee, Wen Hwa; Takahashi, Yoshinori; Wang, Hong-Gang; Minassian, Arlet; Feng, Pinghui; Deretic, Vojo; Pepperkok, Rainer; Tagaya, Mitsuo; Yoon, Ho Sup; Liang, Chengyu.

In: Nature Cell Biology, Vol. 15, No. 10, 01.10.2013, p. 1206-1219.

Research output: Contribution to journalArticle

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T1 - PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 transport by differential interactions with the ER tether and the beclin 1 complex

AU - He, Shanshan

AU - Ni, Duojiao

AU - Ma, Binyun

AU - Lee, Joo Hyung

AU - Zhang, Tian

AU - Ghozalli, Irene

AU - Pirooz, Sara Dolatshahi

AU - Zhao, Zhen

AU - Bharatham, Nagakumar

AU - Li, Baihong

AU - Oh, Soohwan

AU - Lee, Wen Hwa

AU - Takahashi, Yoshinori

AU - Wang, Hong-Gang

AU - Minassian, Arlet

AU - Feng, Pinghui

AU - Deretic, Vojo

AU - Pepperkok, Rainer

AU - Tagaya, Mitsuo

AU - Yoon, Ho Sup

AU - Liang, Chengyu

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N2 - Endoplasmic reticulum (ER)-Golgi membrane transport and autophagy are intersecting trafficking pathways that are tightly regulated and crucial for homeostasis, development and disease. Here, we identify UVRAG, a beclin-1-binding autophagic factor, as a phosphatidylinositol-3-phosphate (PtdIns(3)P)-binding protein that depends on PtdIns(3)P for its ER localization. We further show that UVRAG interacts with RINT-1, and acts as an integral component of the RINT-1-containing ER tethering complex, which couples phosphoinositide metabolism to COPI-vesicle tethering. Displacement or knockdown of UVRAG profoundly disrupted COPI cargo transfer to the ER and Golgi integrity. Intriguingly, autophagy caused the dissociation of UVRAG from the ER tether, which in turn worked in concert with the Bif-1-beclin-1-PI(3)KC3 complex to mobilize Atg9 translocation for autophagosome formation. These findings identify a regulatory mechanism that coordinates Golgi-ER retrograde and autophagy-related vesicular trafficking events through physical and functional interactions between UVRAG, phosphoinositide and their regulatory factors, thereby ensuring spatiotemporal fidelity of membrane trafficking and maintenance of organelle homeostasis.

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